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Translational Research Presentations

(Ordered by start date/time)


Incorporating demographics into a skin cancer diagnosis algorithm for Raman spectroscopy improves diagnostic specificity
Paper 10851-1

Author(s):  Jianhua Zhao, BC Cancer Research Ctr. (Canada), et al.
Conference 10851: Photonics in Dermatology and Plastic Surgery 2019
Session 1: Skin Cancer
Date and Time: 2/2/2019 8:00:00 AM

Raman spectroscopy is a non-invasive optical technique that has been proven to be a promising technique for skin cancer diagnosis. We found that the posterior probability of being a cancer is significantly dependent on gender, age and location of the lesion (p<0.05). The area under the receiver operating characteristic curve (ROC) is increased from 0.905 (95%CI: 0.884-0.927) to 0.932 (95%CI: 0.919-0.945); and the specificity is increased from 43.2% to 50.1% at sensitivity of 99%; and from 73.4% to 77.5% at sensitivity of 90% after taking into account demographics.


The Iphone X as 3D scanner for quantitative photography of faces for diagnosis and treatment follow-up
Paper 10869-1

Author(s):  Rudolf M. Verdaasdonk, Amsterdam UMC (Netherlands), et al.
Conference 10869: Optics and Biophotonics in Low-Resource Settings V
Session 1: Emerging Technologies
Date and Time: 2/2/2019 8:20:00 AM

The Iphone X has a face recognition function that can be used as 3D scanner. The Bellus3D IOS app enables face scanning in 30s with slt export. The resolution of the Iphone X/Bellus3D was tested on face phantoms and compared with high-end 3D scanners using deviation maps. The Iphone X/Bellus3D performed best for the front view of the face with mesh density around 0.6-0.8 mm compared to the Artec scanners (


Pharmacokinetic and pharmacodynamic tomography
Paper 10859-1

Author(s):  Conor L. Evans, Wellman Ctr. for Photomedicine, Massachusetts General Hospital (United States), et al.
Conference 10859: Visualizing and Quantifying Drug Distribution in Tissue III
Session 1: Pharmacokinetic and Pharmacodynamic Tomography I
Date and Time: 2/2/2019 8:20:00 AM

Drug discovery, formulation development, and generic drug development all require detailed knowledge regarding the uptake and action of specific molecules. However, the majority of pharmaceutical agents are small molecules that cannot be tagged with traditional imaging agents without significantly altering both their pharmacokinetics and pharmacodynamics. Advanced microscopy methods, including coherent Raman and fluorescence lifetime imaging, are tools that can overcome these limitations for the quantification of drugs in tissue. We will show that, when paired with image analysis tools, pharmacokinetic tomography can reveal important information on the uptake of topical agents in the skin.


Preoperative evaluation of nonmelanoma skin cancer margins using optical polarization imaging
Paper 10851-2

Author(s):  Anna N. Yaroslavsky, Univ. of Massachusetts Lowell (United States), et al.
Conference 10851: Photonics in Dermatology and Plastic Surgery 2019
Session 1: Skin Cancer
Date and Time: 2/2/2019 8:20:00 AM

The goal of this study was to examine clinical utility of Optical Polarization Imaging (OPI) for preoperative demarcation of the nonmelanoma skin cancers. Patients scheduled for Mohs Surgery participated in the study. Fifty-three lesions on 48 patients were imaged. In thirteen cases requiring more than one Mohs stage to completely remove the cancer, the optical images correctly identified tumor involvement beyond the surgeon’s markings. Our results demonstrate that OPI offers a noninvasive real time tool for cancer margin demarcation.


High-resolution micro-OCT for endothelial cell visualization in the coronary arteries
Paper 10855-1

Author(s):  Osman O. Ahsen, Massachusetts General Hospital (United States), et al.
Conference 10855: Diagnostic and Therapeutic Applications of Light in Cardiology 2019
Session 1: OCT
Date and Time: 2/2/2019 8:30:00 AM

The study of endothelial cells (ECs) in humans remains elusive because of a lack of an imaging tool with sufficient resolution. In this study, we investigated the capability of a novel form of OCT with a resolution of 1 µm, termed µOCT, to visualize EC morphology. µOCT enabled clear visualization of ECs pavementing that was seen by scanning electron microscopy. µOCT also showed the capability of identifying EC morphology of human coronary plaque harboring leukocyte adhesion and EC stent strut tissue coverage. µOCT could be useful to better understand the role of ECs in the pathogenesis of coronary artery disease.


Real-time label-free multimodal multiphoton imaging for assessing the intraoperative tumor microenvironment
Paper 10862-1

Author(s):  Stephen A. Boppart, Univ. of Illinois (United States), et al.
Conference 10862: Molecular-Guided Surgery: Molecules, Devices, and Applications V
Session 1: Advanced Detection Methods I
Date and Time: 2/2/2019 8:30:00 AM

Label-free intravital imaging and imaging of fresh, unstained, resected tissue specimens during surgery offers a wealth of new biomarkers for assessing the tumor microenvironment and diagnosing disease. By generating new excitation wavelengths and manipulating the light stimulus in new ways, Simultaneous Label-free Auto-fluorescence Multi-harmonic (SLAM) microscopy can achieve fast and simultaneous visualization of the rich intrinsic molecular, metabolic, and structural information. These results suggest the broad potential of this stain-free, slide-free, technology and methodology for real-time intraoperative molecular-guided surgical applications.


Differential artery-vein analysis in optical coherence tomography angiography
Paper 10858-1

Author(s):  Minhaj Nur Alam, Univ. of Illinois at Chicago (United States), et al.
Conference 10858: Ophthalmic Technologies XXIX
Session 1: Angiography and Blood Flow I
Date and Time: 2/2/2019 8:30:00 AM

It is known that diabetic retinopathy (DR) can affect arteries and veins differently. Therefore, reliable differentiation of arteries and veins is essential for classifying DR stages. This project was designed to develop a method for quantitative analysis of arteries and veins in optical coherence tomography angiography (OCTA) images, and to verify that differential artery-vein analysis can improve the sensitivity of quantitative OCTA features for objective identification of DR. We report here color fundus image guided artery-vein differentiation in OCTA, and introduce AVR-BVC as an objective metric for DR detection and classification.


Non-invasive label-free three-dimensional volumetric Multispectral Optoacoustic Tomography (vMSOT) visualization of non-melanoma skin cancers
Paper 10851-3

Author(s):  Ghayathri Balasundaram, Singapore Bioimaging Consortium (Singapore), et al.
Conference 10851: Photonics in Dermatology and Plastic Surgery 2019
Session 1: Skin Cancer
Date and Time: 2/2/2019 8:40:00 AM


Reversible blood-brain barrier modulation enhances in vivo delivery of panitumumab-IRDye800 to high-grade glioma in cranial window model
Paper 10864-1

Author(s):  Quan Zhou, Stanford Univ. (United States), et al.
Conference 10864: Clinical and Translational Neurophotonics 2019
Session 1: Operative and Post Operative Therapy I
Date and Time: 2/2/2019 8:50:00 AM

Pediatric high-grade gliomas (pHGGs) are malignant brain tumors that kill more children than any other cancer type. pHGGs typically have irregular shapes and ill-defined margins as they actively grow and invade into surrounding normal brain. Since the extent of surgical resection predicts survival, precise tumor removal with more accurate margin detection means better treatment outcome and longer survival for patients. The goal of this study is to provide a solution to visually guide pHGG resection with antibody-based imaging molecules known to be safe for humans and target a specific biomarker (EGFR) of pHGG. A three-fold improvement in brain permeability was achieved following siRNA-induced temporary opening of the blood-brain barrier, a major obstacle for drug delivery into the brain. As a result, 74% increase in contrast enhancement in brain tumor was observed in live mice 48 hours later through a preinstalled glass window in the their skull. Applying this strategy in image-guided surgery could potentially benefit 70% of pHGG patients as we found preferential presence of EGFR biomarker in teenage subpopulation of the disease over one that is younger than one year old.


Quantitative assessment of tympanic membrane mobility during otitis media using pneumatic OCT
Paper 10853-2

Author(s):  Jungeun Won, Univ. of Illinois at Urbana-Champaign (United States), et al.
Conference 10853: Optical Imaging, Therapeutics, and Advanced Technology in Head and Neck Surgery and Otolaryngology 2019
Session 1: Optical Technologies for Assessment and Guidance of Middle and Inner Ear Structures and Beyond
Date and Time: 2/2/2019 8:50:00 AM

To quantitatively investigate tympanic membrane (TM) mobility during otitis media (OM), a handheld pneumatic OCT system was employed to non-invasively capture pneumatic-induced movements of the TM. A computer-controlled pressure transient of 150 daPa at 1-2 Hz was generated via an activated voice coil and bellows. Healthy subjects and subjects with OM were recruited at Carle Foundation Hospital (Urbana, IL). The dynamics of the TM in response to pressure transients delivered to the sealed ear canal were measured and statistically compared, in addition to the spatial and temporal variances of the pneumatic-induced TM mobility.


Imaging atrioventricular nodal conduction tissue in porcine heart with polarization-sensitive optical coherence tomography
Paper 10855-4

Author(s):  Xiaowei Zhao, Case Western Reserve Univ. (United States), et al.
Conference 10855: Diagnostic and Therapeutic Applications of Light in Cardiology 2019
Session 1: OCT
Date and Time: 2/2/2019 9:10:00 AM

Radiofrequency ablation (RFA) is a preferred invasive treatment modality for atrioventricular nodal reentrant tachycardia (AVNRT) due to high efficiency and low complication rate. However, because culprit tissue is close to atrioventricular nodal (AVN) tissue, and there is no direct tissue substrate guidance of the procedure, RFA suffers from a high complication rate (atrioventricular block). This risk indicates an unmet need to locate and protect the AVN tissue during treatment to increase safety and efficiency. Benchtop polarization-sensitive optical coherence tomography was used to identify the AVN tissue of porcine hearts and may potentially guide AVNRT treatment in the future.


Correlation of optical coherence elastography with clinical evaluation of systemic sclerosis
Paper 10880-3

Author(s):  Chih-Hao Liu, Univ. of Houston (United States), et al.
Conference 10880: Optical Elastography and Tissue Biomechanics VI
Session 1: Optical Coherence Elastography I
Date and Time: 2/2/2019 9:15:00 AM

Systemic sclerosis (SSc) is a rare connective tissue disease that has a high mortality rate. Currently, the modified Rodnan skin score (mRSS) is the gold standard for evaluating SSc progression. However, the mRSS procedure can be time consuming, and is a source of significant subjective bias. In this work, we demonstrated the first use of air-pulse based OCE for SSc detection in patients, with comparison to standard clinical diagnostic methods. The results show that OCE corroborated the clinical findings, and demonstrate that OCE is a promising technology for objectively and noninvasively detecting SSc.


Predicting antibody penetration in a first-in-human clinical trial of head and neck cancers
Paper 10859-4

Author(s):  Guolan Lu, Stanford Univ. (United States), et al.
Conference 10859: Visualizing and Quantifying Drug Distribution in Tissue III
Session 1: Pharmacokinetic and Pharmacodynamic Tomography I
Date and Time: 2/2/2019 9:20:00 AM

Low response rates in solid tumors including head and neck cancers have been attributed to failure of the drug to reach its intended target. However, investigation of drug delivery has been limited due to difficulties in measuring concentrations in the tumor and the ability to localizing drugs in human tissues. Factors determining antibody distribution in primary tumor and metastatic lymph nodes have not been well-studied in human patients. To address this challenge, we propose to leverage fluorescently labeled antibodies to investigate intratumoral antibody delivery. We developed quantitative methods to measure intratumoral drug concentration and predictive pipeline to predict antibody penetration.


Real time large scale air flow imaging for qualitative measurements in view of infection control in the OR
Paper 10870-1

Author(s):  Rudolf M. Verdaasdonk, Amsterdam UMC (Netherlands), et al.
Conference 10870: Design and Quality for Biomedical Technologies XII
Session 1: Enhanced Imaging and Spectroscopy
Date and Time: 2/2/2019 9:30:00 AM

To prevent contaminations and infections, precautions are taken in an OR environment. However, this controlled environment can easily be disturbed by medical equipment with internal cooling fans. In progress of a previous study, a special large field air flow visualization technique has been adapted to study and quantify the air flow around equipment in real-time by digital subtraction of a fine line pattern in the background. Due to the real-time visualization, the instant effect of e.g. repositioning equipment is observed. The awareness of the disturbance of the laminar air flow should lead to guidelines to improve the design and positioning of medical equipment in the OR to reduce infections.


High-definition intravascular optical coherence tomography catheter design
Paper 10855-5

Author(s):  Zhonglie Piao, Massachusetts General Hospital (United States), et al.
Conference 10855: Diagnostic and Therapeutic Applications of Light in Cardiology 2019
Session 1: OCT
Date and Time: 2/2/2019 9:30:00 AM


Intra-spinal irradiation distribution associated with local light delivery as measured in a pilot rabbit model: Implications toward epidural photo-neuro-modulation of the spinal cord
Paper 10861-4

Author(s):  Daqing Piao, Oklahoma State Univ. (United States), et al.
Conference 10861: Mechanisms of Photobiomodulation Therapy XIV
Session 1: PBM Mechanisms I
Date and Time: 2/2/2019 9:35:00 AM

Photobiomodulation therapy (PBMT) has been shown in rodent models to stimulate axonal growth of the spinal cord after acute structural damage. However, the existing clinical protocols of surface irradiation results in significant treatment dose attenuation by the vertebral bones as the PBMT light travels to the level of the spinal cord. A pilot testing in a rabbit model showed that


Exploring the connection between innate immunity and hemodynamics during cancer treatments using diffuse and nonlinear optical imaging
Paper 10888-4

Author(s):  Darren M. Roblyer, Boston Univ. (United States), et al.
Conference 10888: Biophysics, Biology and Biophotonics IV: the Crossroads
Session 1: Optogenetics, Opto-immunology, and Opto-oncology I
Date and Time: 2/2/2019 9:40:00 AM

Some chemotherapeutics are known to induce immunogenic cell death, a process that induces immunostimulation of the tumor and host and potentiates the direct cytotoxic effects of these drugs. Our multi-disciplinary research team is exploring immunogenic cell death at the molecular, cellular, and whole organism levels. We have developed a suite of preclinical and clinical optical imaging technologies that allow us to probe how the innate immune response is linked to hemodynamic changes observed during treatment. This talk will highlight our most recent technological developments and biological findings, as well as the clinical data that inspired this avenue of research.


Sensitivity analysis multibranched light guide for real time hyperspectral imaging system
Paper 10871-6

Author(s):  Craig M. Browning, Univ. of South Alabama (United States), et al.
Conference 10871: Multimodal Biomedical Imaging XIV
Session 1: Multimodal Microscopy
Date and Time: 2/2/2019 9:40:00 AM

Hyperspectral imaging (HSI) collects spectroscopic data providing molecular composition, per pixel, in fields such as satellite imagery, food quality or archaeology. This work applies HSI to medical screenings for example, endoscopic procedures and live cell imaging. Here we present a prototype LED spectral light source containing a multi-branched solid light guide coupled to a commercial colonoscope allowing for sub-video rates (8 fps). Here, we present a parametric analysis to decrease transmission losses (98% on the first prototype) by increasing optical throughput (i.e. focusing lens to collect more of the LED viewing angle) for standard video rates enabling endoscopic hyperspectral imaging.


Non-contact fluorescence tomography using a cone-beam CT surgical guidance system
Paper 10862-5

Author(s):  Michael J. Daly, Princess Margaret Cancer Ctr. (Canada), et al.
Conference 10862: Molecular-Guided Surgery: Molecules, Devices, and Applications V
Session 1: Advanced Detection Methods I
Date and Time: 2/2/2019 9:45:00 AM

To exploit fully the clinical potential of molecular fluorescence contrast agents, there is growing interest in the development of quantitative fluorescence imaging systems for surgical use. Here, we leverage cone-beam CT (CBCT) imaging and surgical navigation technology to generate spatial priors for diffuse optical fluorescence tomography (DOFT). A software pipeline is described to incorporate imaging and localization data for tetrahedral mesh generation, non-contact surface flux mapping, and sub-surface region segmentation. Liquid phantom experiments quantified the benefits of spatial priors over an unguided approach. An in vivo animal model demonstrated system performance for tumour delineation using a multi-modal liposomal agent.


Flexible plasmonic sensors for wearables and one-time use assays
Paper 10869-7

Author(s):  Zachary S. Ballard, Univ. of California, Los Angeles (United States), et al.
Conference 10869: Optics and Biophotonics in Low-Resource Settings V
Session 1: Emerging Technologies
Date and Time: 2/2/2019 10:00:00 AM

Localized Surface Plasmon Resonance (LSPR) sensors have been shown to be highly sensitive label-free molecular sensors. Recently, emerging fabrication techniques have produced flexible LSPR sensors, which can possibly be implemented in wearables or as disposable, one-time-use assays. In this work, we demonstrate a ‘transfer-printing’ technique where flexible plasmonic sensors are adhered to other wearable substrates such as a contact lenses or bandages, where they could potentially sample key bio-molecules non-invasively for quantification with a handheld device. Taken together, such sensing systems could have impact on diagnostics, personalized medicine, or at-home health monitoring.


Label-free, morpho-functional two-photon imaging enables accurate classification of cervical pre-cancers
Paper 10856-5

Author(s):  Irene Georgakoudi, Tufts Univ. (United States), et al.
Conference 10856: Diseases in the Breast and Reproductive System V
Session 1: Obstetrics and Gynecology
Date and Time: 2/2/2019 10:10:00 AM

We used label-free, two photon microscopy to collect NADH and FAD depth-dependent images of 25 freshly excised cervical tissue biopsies. We analyzed these images to extract a combination of: a) morphological tissue metrics, such as epithelial thickness and the nuclear to cytoplasmic ratio, and b) functional metabolic tissue metrics, including the redox ratio, mitochondrial clustering, and their heterogeneity within a field or across the epithelial depth. A combination of six corresponding metrics was identified using quadratic discriminant analysis to confer optimal classification performance which exceeded 90% sensitivity and 80% specificity for HSIL vs. non-HSIL tissues.


Time-Resolved Optical Monitoring to detect and identify deep flaps
Paper 10862-6

Author(s):  Jean-Luc Coll, INSERM (France), et al.
Conference 10862: Molecular-Guided Surgery: Molecules, Devices, and Applications V
Session 2: Advanced Detection Methods II
Date and Time: 2/2/2019 10:30:00 AM

Near Infrared Spectroscopy (NIRS) is noted as a noninvasive, cheap, continuous monitoring tool that provides excellent positive and negative predictive values, leading to an improvement of flap salvage. Nevertheless, it is unable to monitor deep layers in the tissue without very large distance between source and detector which is impossible in some configurations. Time-Resolved approach allows us to address such buried flaps. To do so, we developed a Time-Resolved (TR) system and a specific optical stethoscope probe that works in the 750-800 and 850nm wavelengths. This system was tested on 32 pigs bearing abdominal flaps buried on the left lateral abdominal muscle (~1cm deep of skin, fat and highly absorbing muscle). Arterial or venous occlusions were performed and we monitored the blood oxygenation in the flaps using our TR system and compared it with NIRS or LICOX measurements (that measure the tissue pressure in Oxygen, Integra laboratory). Our results show that while the detection of occlusion depends on its depth in NIRS, we were able to detect occlusions whatever the sample (from the surface down to 1.23 mm) using the Resolved Time signals. In addition, the Oxy and Deoxy concentrations information provided by TR made it possible to identify the type of occlusion, which LICOX does not always allow. Acknowledgement: This study is made possible by the support of the ANR FLAPS Monitoring ANR-15-CE19_0010 (Agence Nationale de Recherche, France).


Duodenal imaging by tethered capsule OCT endomicroscopy in adolescents with environmental enteric dysfunction
Paper 10854-7

Author(s):  Jing Dong, Wellman Ctr. for Photomedicine (United States), et al.
Conference 10854: Endoscopic Microscopy XIV
Session 2: Endoscopic OCT
Date and Time: 2/2/2019 10:30:00 AM

Environmental Enteric Dysfunction (EED) is a condition that has minimal acute symptoms but many chronic problems with absorbing nutrients that lead to malnutrition and growth stunting in children. EED also results in a number of changes in the intestines that include villous blunting, increased permeability, bacterial translocation, and inflammation. In this abstract, we report on a duodenal imaging study in adolescents with EED at Aga Khan Medical Center in Pakistan that uses a new generation tethered capsule OCT endomicroscopy technology to evaluate duodenal morphology. Results showed that Pakistan subjects had shorter villous lengths and larger widths in comparison to those imaged in controls from the US.


Differentiation of healthy and malignant brain tissues using terahertz pulsed spectroscopy and optical coherence tomography
Paper 10864-5

Author(s):  Nikita V. Chernomyrdin, Bauman Moscow State Technical Univ. (Russian Federation), et al.
Conference 10864: Clinical and Translational Neurophotonics 2019
Session 2: Operative and Post Operative Therapy II
Date and Time: 2/2/2019 10:40:00 AM

Intraoperative diagnosis of brain tumors remains a challenging problem of modern neurosurgery. A complete resection of tumor is the most important factor, determining an efficiency of its treatment, while an incomplete resection (due to inaccurate detection of tumor margins) increases the probability of tumor recurrence. We studied a potential of optical coherence tomography (OCT) and terahertz (THz) spectroscopy, in intraoperative diagnosis of brain gliomas (grade II to IV). We measured and analyzed the THz responses and OCT images of intact and pathological tissues ex vivo. The observed results promise novel applications of THz technology and OCT in label-free intraoperative neurodiagnosis.


Fluorescence lifetime imaging microscopy along with non-Euclidean phasor analysis for visualization of drug distribution of a topical drug in human facial skin
Paper 10859-7

Author(s):  Sinyoung Jeong, Massachusetts General Hospital (United States), et al.
Conference 10859: Visualizing and Quantifying Drug Distribution in Tissue III
Session 2: Pharmacokinetic and Pharmacodynamic Tomography II
Date and Time: 2/2/2019 10:50:00 AM

Understanding a drug candidate’s pharmacokinetics and pharmacodynamics (PK/PD) is a challenging but essential aspect of drug development. Investigation of the penetration and distribution of a topical drug’s active pharmaceutical ingredient (API) allows for evaluation of delivery and effectiveness. Recently, we have developed a method for selectively visualizing the drug distribution of topical minocycline gel (BPX-01) within ex vivo human facial skin using two-photon fluorescence lifetime imaging microscopy with non-Euclidean phasor analysis. BPX-01 is developed to effectively treat moderate to severe acne vulgaris by directly delivering the minocycline to the pilosebaceous unit through the skin barrier. Since minocycline is naturally fluorescent and has a distinct fluorescence lifetime compared to skin, the distribution of minocycline within skin can be selectively visualized. This demonstrated that daily recommended dosage of BPX-01 was able to be delivered to the pilosebaceous unit through hair follicles. Retinoids have also been widely utilized to treat acne as a topical therapy. In order to improve the efficacy of topical drug delivery toward the treatment of inflammatory acne, a topical gel was developed by combining a topical antibiotic (minocycline) and a retinoid. Since retinoids can have distinct fluorescence lifetimes from skin and minocycline, we were able to selectively visualize the distribution of minocycline and the retinoid within skin, while isolating the contributions of the three components in FLIM phasor analysis. Based on our results, we were able to verify the applicability of our visualization method for multicomponent PK/PD study with subcellular resolution and molecular specificity.


Compact low-cost briefcase OCT system with automated classification for point-of-care diagnosis of otitis media
Paper 10869-8

Author(s):  Roshan Dsouza, Univ. of Illinois (United States), et al.
Conference 10869: Optics and Biophotonics in Low-Resource Settings V
Session 2: Tomographic Methods
Date and Time: 2/2/2019 10:50:00 AM

We report a portable, low-cost, briefcase optical coherence tomography (OCT) system with automated classification for point-of-care diagnosis of otitis media (OM). The briefcase OCT system cost < $8000USD, a 5-fold cost reduction, and a 3-fold size reduction compared to standard OCT systems. Additionally, this system utilizes unique real-time mosaicking of surface video images that are synchronized with rapid A-scan acquisition, and enable computationally generated thickness maps and construction of cross-sectional B-mode images over extended lateral distances. Furthermore, a random-forest based classifier is utilized with an expanded feature set based on various statistics and metrics derived from OCT A-lines and B-scans.


Endobronchial optical coherence tomography for in vivo microscopic assessment and diagnosis of fibrotic lung disease
Paper 10854-8

Author(s):  Lida P. Hariri, Massachusetts General Hospital (United States), et al.
Conference 10854: Endoscopic Microscopy XIV
Session 2: Endoscopic OCT
Date and Time: 2/2/2019 10:50:00 AM

Idiopathic pulmonary fibrosis (IPF) requires diagnostic certainty to stratify prognosis and therapeutic decision-making. Often, patients must undergo surgical tissue resection for diagnosis, which has risks of adverse effects. Endobronchial OCT has potential to provide a low-risk, non-surgical method for IPF diagnosis. We conducted in vivo endobronchial OCT in ILD patients undergoing diagnostic biopsy. OCT and biopsy interpretations were performed independently, and compared. Endobronchial OCT was able to identify IPF and non-IPF ILD in patients with non-diagnostic HRCT. We conclude that OCT has potential as a minimally-invasive method for IPF diagnosis.


Fluorescence lifetime imaging of protoporphyrin IX using a modulated time of flight camera for brain cancer diagnosis
Paper 10862-7

Author(s):  Mikael T. Erkkilä, Ctr. for Medical Physics and Biomedical Engineering, Medizinische Univ. Wien (Austria), et al.
Conference 10862: Molecular-Guided Surgery: Molecules, Devices, and Applications V
Session 2: Advanced Detection Methods II
Date and Time: 2/2/2019 11:00:00 AM

Fluorescence guided surgery, especially aminolevulinic acid induced protoporphyrin IX, has had significant impact for improving the gross total resection of gliomas. The fluorescence is mainly observed visually by the surgeon, and tissue properties like specular reflections or scattering may hide malign tissue which is then left untreated. To overcome these limitations, we propose using fluorescence lifetime imaging of protoporphyrin IX detected via a modulated time-of-flight camera. Here the fluorophore acts as a molecular sensor and can be used to investigate its chemical microenvironment. Tissue phantoms and ex-vivo human brain cancer biopsies were imaged providing additional information compared to intensity-based imaging.


Endoscopic optical coherence tomography for sublayer measurement of the human oral mucosa in vivo
Paper 10854-9

Author(s):  Julia Walther, TU Dresden (Germany), et al.
Conference 10854: Endoscopic Microscopy XIV
Session 2: Endoscopic OCT
Date and Time: 2/2/2019 11:10:00 AM

The clinical diagnosis of early alterations of the oral mucosa remains challenging, for which reason the demand for supportive diagnostic systems arises. Optical biopsy can be an adjunct approach for diagnosing oral tissue alterations non-invasively. Here, optical coherence tomography (OCT) is used for examining healthy human oral mucosa in ten different regions of the oral cavity and oropharynx by means of a volunteer study. The obtained data are used for segmentation and classification of the mucosal layers providing the basis for the quantification of objective parameters of the epithelial and connective tissue layers such as reflectivity, homogeneity and thickness.


Label-free optical detection grading and staging of urothelial carcinoma through multimodal fibre-probe spectroscopy
Paper 10852-5

Author(s):  Enrico Baria, Istituto Nazionale di Ottica (Italy), et al.
Conference 10852: Therapeutics and Diagnostics in Urology 2019
Session 2: Imaging
Date and Time: 2/2/2019 11:20:00 AM

Optical spectroscopy techniques can provide fast, label-free and non-invasive alternatives to standard histopathology for assessing both grade and stage of urothelial carcinoma (UC). Thus, we combined auto-fluorescence, diffuse reflectance and Raman spectroscopy in a compact and transportable setup based on an optical fibre-probe. This experimental setup was used for studying fresh biopsies of urothelial tumour and healthy bladder collected from 49 patients undergoing Transurethral Resection of Bladder Tumours. Multimodal spectroscopy provided high-sensitivity, high-specificity discriminating capability for UC detection, grading and staging. The obtained results were generated in a fast and label-free way, offering the potential for endoscopic in vivo applications.


Quantitative cross-polarization OCT image analysis of ex vivo human brain tissues and its comparison with MRI and histological data
Paper 10864-7

Author(s):  Elena B. Kiseleva, Privolzhsky Research Medical Univ. (Russian Federation), et al.
Conference 10864: Clinical and Translational Neurophotonics 2019
Session 2: Operative and Post Operative Therapy II
Date and Time: 2/2/2019 11:20:00 AM

OCT is a perspective method for glial tumor margins detection during surgical operation. This study aimed to evaluate cross-polarization (CP) OCT feasibility to distinguish different types of brain tissue during glioma surgery to assess tumor margins and the proximity to the conductive pathways of the brain. It was shown, that the quantitative characteristics of the CP OCT signal of the tumor and peritumoral area have quite good correspondence with the tumor location according to the preoperative MRI, and better correlated with histological data. The same results were demonstrated for comparison of the CP OCT signal of the peritumoral areas and the normal white matter with the MRI-tractography and histological data.


Real-time, label-free, intraoperative visualization of peripheral nerves and micro-vasculatures using multimodal optical imaging techniques
Paper 10871-9

Author(s):  Jaepyeong Cha, Children's National Health System (United States), et al.
Conference 10871: Multimodal Biomedical Imaging XIV
Session 2: Surgical Guidance
Date and Time: 2/2/2019 11:20:00 AM

Real-time identification and display of critical anatomic structures, such as the nerve and vasculature structures, are critical for reducing complications and improving surgical outcomes. Human vision is limited in clearly contrasting these structures. Here, we present a novel multimodal optical imaging system, which enables noninvasive visualization of these critical anatomic structures during surgical dissection. Peripheral nerves are visualized by a snapshot polarimetry that calculates the anisotropic optical properties. Vascular structures, both venous and arterial, are monitored in real-time using a near-infrared laser-speckle-contrast imaging. We evaluate the system by performing in vivo animal studies with comparison by contrast-agent-aided fluorescence imaging.


Fluorescence lifetime imaging and intravascular ultrasound (FLIm/IVUS) platform for label-free intraluminal characterization of vascular biomaterials in vitro and in vivo
Paper 10855-9

Author(s):  Alba Alfonso García, Univ. of California, Davis (United States), et al.
Conference 10855: Diagnostic and Therapeutic Applications of Light in Cardiology 2019
Session 2: Imaging and Vascular Materials
Date and Time: 2/2/2019 11:20:00 AM

A fiber-based, label-free multispectral fluorescence lifetime imaging and intravascular ultrasound (FLIm/IVUS) system was evaluated as a novel diagnostic tool for monitoring variations in biochemical and structural composition of vascular biomaterials, including native arteries and engineered vascular grafts both in vitro and in vivo. We performed in vitro evaluation of pig carotid arteries and determined correlations between FLIm parameters and biochemical composition. Additionally, spectral and lifetime differences between native carotid arteries and engineered vascular grafts were examined. Finally, we performed in vivo imaging of engineered graft implanted in healthy pig carotid artery with fiber-based FLIm/IVUS to demonstrate the versatility of the fiber-based instrument.


Investigating the potential role of endoscopic PS-OCT in monitoring bronchial thermoplasty for the treatment of asthma
Paper 10854-10

Author(s):  David C. Adams, Massachusetts General Hospital (United States), et al.
Conference 10854: Endoscopic Microscopy XIV
Session 2: Endoscopic OCT
Date and Time: 2/2/2019 11:30:00 AM

Bronchial thermoplasty (BT) aims to reduce the symptoms of asthma by ablating the hyper-responsive airway smooth muscle (ASM), but has met with mixed outcomes. In this work we present the results of a study in which we imaged canines before and after BT using polarization-sensitive optical coherence tomography (PS-OCT) in order to assess the potential of PS-OCT for use in conjunction with the BT procedure. Correlations with histology demonstrate the accuracy of our imaging, while volumetric representations demonstrate the varying effectiveness of the procedure. We believe this study demonstrates the potential of PS-OCT for complementing therapies such as BT.


Pharmacokinetics of small molecule drugs in skin studied with coherent Raman imaging and deep learning
Paper 10859-9

Author(s):  Amin Feizpour, Wellman Ctr. for Photomedicine, Massachusetts General Hospital (United States), et al.
Conference 10859: Visualizing and Quantifying Drug Distribution in Tissue III
Session 2: Pharmacokinetic and Pharmacodynamic Tomography II
Date and Time: 2/2/2019 11:35:00 AM

Coherent Raman Imaging (CRI) is a non-destructive and label-free optical imaging technique that allows for chemically-selective tissue imaging without the need for exogenous labels. In this study, we have utilized CRI to image the 3D distribution and kinetics of small molecule drugs in ex-vivo mouse skin, in addition to the tomography of the tissue, with sub-cellular resolution. To quantify skin pharmacokinetics, we have developed deep learning (DL) algorithms, based on Tensorflow and Deep Convoluted Neural Networks, that are able to extract tissue drug concentrations via DL-based segmentation. I will present the imaging technique, image processing and analysis approaches, in addition to the results of our studies on the pharmacokinetic behavior of different vehicles and drugs in the skin.


An innovative passive computer vision solution for flexible cystoscopic image reconstruction
Paper 10852-6

Author(s):  Sorush Ranjbar, The Univ. of Texas at San Antonio (United States), et al.
Conference 10852: Therapeutics and Diagnostics in Urology 2019
Session 2: Imaging
Date and Time: 2/2/2019 11:40:00 AM

The need for innovative technologies to monitor the urinary bladder is motivated by the prevalence and high recurrence rates of bladder cancer. The flexible cystoscopy remains the gold standard for the diagnosis and treatment of bladder disease. Cystoscopic data, which can contain important structural information, is frequently discarded after a cystoscopy procedure. We use this data in conjunction with computer vision techniques to obtain 3D point clouds of the surface of the bladder. The point cloud is processed into a 3D surface mesh. Work is underway to deploy this computer vision pipeline in a clinical setting.


Direct in situ visualization of cancer-associated extracellular vesicles by simultaneous label-free autofluorescence multiharmonic (SLAM) microscopy
Paper 10856-8

Author(s):  Sixian You, Univ. of Illinois (United States), et al.
Conference 10856: Diseases in the Breast and Reproductive System V
Session 2: Breast Cancer Biology
Date and Time: 2/2/2019 11:40:00 AM

Direct visualization and characterization of cancer-associated extracellular vesicles (EVs) is highly desired for cancer research, but currently lacking. In this work, by using simultaneous label-free autofluorescence multiharmonic (SLAM) microscopy, we fully utilize the intrinsic metabolic and structural properties of EVs and demonstrate reliable visualization of EVs in validated fractioned EV samples, living cells and animals, and fresh human tissues. Analysis of individual vesicular content reveals highly concentrated NAD(P)H in EVs from cancerous tissue. This unique optical signature is then used for identification of cancer EVs in human breast cancer, and their density is highly correlated with clinical diagnosis.


Convolutional neural networks in melanoma detection using spatial and spectral domain
Paper 10851-10

Author(s):  Ilkka Pölönen, Univ. of Jyväskylä (Finland), et al.
Conference 10851: Photonics in Dermatology and Plastic Surgery 2019
Session 4: Machine Learning II
Date and Time: 2/2/2019 11:40:00 AM

In this study we will demonstrate difference between using just spectral domain and both the spectral and spatial domain as a feature space for the separation of four lesion classes (malignant melanomas, melanoma in-situs, dysplastic nevi and bening nevi). Classification from both cases uses convolutional neural networks. Results are cross-validated using leave-one-out methodology. Our data set (n=64) consist of hyperspectral images covering narrow wavebands from 450 to 850 nm. After imaging lesions were diagnosed by histopathology.


Statistical multivariate analysis of biomarkers for circulating tumor cell detection
Paper 10889-9

Author(s):  Emily A. Gibson, Univ. of Colorado Denver (United States), et al.
Conference 10889: High-Speed Biomedical Imaging and Spectroscopy IV
Session 3: Novel High-speed Applications
Date and Time: 2/2/2019 1:30:00 PM

Detection of circulating tumor cells with image cytometry is limited by the sensitivity and specificity of the biomarker panel. We collected confocal images of ~100,000 cells labeled for DNA, lipids, CD45, and Cytokeratin on a model system of MCF7 and WBCs representing disease positive, D+ and disease negative, D- populations. We computed spatial image metrics and performed multivariable regression and feature selection, increasing the separation of the D+ and D- populations to 7 standard deviations with detection limit of ~1 in 480. In conclusion, simple regression analysis holds promise to improve the separation of rare cells in cytometry applications.


Intraoperative surgical guidance using label-free fluorescence lifetime imaging and augmented reality visualization
Paper 10862-11

Author(s):  Laura Marcu, Univ. of California, Davis (United States), et al.
Conference 10862: Molecular-Guided Surgery: Molecules, Devices, and Applications V
Session 3: Imaging Systems
Date and Time: 2/2/2019 1:30:00 PM

This presentation overviews clinically-compatible multispectral fluorescence lifetime imaging (FLIM) techniques developed in our laboratory and their ability to operate as stand-alone tools, integrated in a biopsy needle and in conjunction with the da Vinci surgical robot. We present clinical studies in patients undergoing surgery that demonstrate the potential of these techniques for intraoperative delineation of brain tumors and brain radiation necrosis as well as head and neck cancer including image-guided augmented reality during trans-oral robotic surgery (TORS). Challenges and solutions in the clinical implementation of these techniques are discussed.


In vivo assessment of inflammation in atherosclerosis and vascular injury by high-resolution intravascular OCT-NIRF molecular imaging
Paper 10855-11

Author(s):  Zhonglie Piao, Massachusetts General Hospital (United States), et al.
Conference 10855: Diagnostic and Therapeutic Applications of Light in Cardiology 2019
Session 3: Multimodal Imaging
Date and Time: 2/2/2019 1:40:00 PM

Dual-modality intravascular optical coherence tomography (OCT) combined with near-infrared fluorescence (NIRF) imaging has been developed to enable simultaneous comprehensive morphologic and molecular assessment of coronary disease. In this study, we will present a high-resolution (HR)-OCT-NIRF imaging technology that enabled three times higher NIRF resolution (< 30 µm) compared to prior-generation OCT-NIRF technology. The system was used to image atherosclerosis in New Zealand white rabbits at 12 weeks after aortic balloon injury and cholesterol feeding. VM110 (ProSense) was injected 24 hours before in vivo aortic imaging. The results indicate that this new HR-OCT-NIRF imaging approaches potentially providing enhanced capability for molecular phenotyping of atherosclerosis and stent-induced vascular injury.


Long lived intralipid-infused tissue phantoms: control and characterization of scattering characteristics
Paper 10876-12

Author(s):  Glenn H. Chapman, Simon Fraser Univ. (Canada), et al.
Conference 10876: Optical Interactions with Tissue and Cells XXX
Session 3: Optical Properties of Tissues II
Date and Time: 2/2/2019 1:40:00 PM

Ongoing work has created tissue phantoms with long lifetime stability (over 6 year) using an intralipid-infused agar encapsulated in clear polymer. Varying the intralipid concentration allows control of the scattering parameters with typical values of µs = 20/cm, g=0.95. These were characterized using a laser beams passing through the test phantoms, observed with a digital camera giving over 8 million measurements over +/- 12 deg. The analysis program showed best results with a Henyey-Greenstein two-term model


Potentials of noninvasive low-level laser therapy for neonatal thrombocytopenia
Paper 10861-8

Author(s):  Mei X. Wu, Harvard Medical School (United States), et al.
Conference 10861: Mechanisms of Photobiomodulation Therapy XIV
Session 3: PBM Mechanisms III
Date and Time: 2/2/2019 1:55:00 PM

Neonatal thrombocytopenia could increase a risk of hemorrhage, especially within the brain and adversely affect its development. Low-level laser treatment (LLLT) is very safe, like blue-light-mediated treatment of newborn jaundice that has been used in clinics for decades. We found that LLLT stimulated the expression of a group of genes involved in mitochondrial generation in megakaryocytes (MKs) in our previous study. We demonstrate in the current study that LLL enhances platelet production and the number of MKs in the liver and bone marrow in newborn mice. The results suggest a potential for LLLT to manage neonatal thrombocytopenia.


Looking to the innate immune system for imageable biomarkers of PDT response
Paper 10860-6

Author(s):  Theresa M. Busch, Univ. of Pennsylvania (United States), et al.
Conference 10860: Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXVIII
Session 3: Photodynamic Therapy III
Date and Time: 2/2/2019 2:00:00 PM

Photodynamic therapy (PDT) can promote a strong inflammatory response that is characterized by the recruitment and activation of innate immune cells such as neutrophils. The activation of innate immunity can contribute to therapeutic outcome, especially under PDT conditions with suboptimal direct cytotoxicity. Yet, in addition to promoting anti-tumor immunity, innate immune response can also induce immunosuppressive cell types such as myeloid derived suppressor cells. Thus, a dual role exists for innate immune activation by PDT. In the context of intraoperative PDT for mesothelioma, we have undertaken preclinical studies of monitoring neutrophil activation by PDT and explored how the time course of this activation associates with long term treatment outcome.


Ultra-fast multiphoton microscopy for diagnostic histology with polygon, stage-scanning, and ultra-high repetition laser
Paper 10889-10

Author(s):  Richard Torres, Yale School of Medicine (United States), et al.
Conference 10889: High-Speed Biomedical Imaging and Spectroscopy IV
Session 3: Novel High-speed Applications
Date and Time: 2/2/2019 2:00:00 PM

Imaging excised tissue specimens while avoiding manual histology processing steps could improve efficiency and quality of clinical diagnoses. A critical limitation of point scanning systems for clinical use is speed. In this analysis we have built upon our recent development of a multiphoton microscope capable of tissue imaging at depth for primary diagnosis at more than 30-times faster than a traditional galvanometer-based system by incorporating a newly-produced 250 MHz ultra-fast laser in a polygon-based instrument with stage scanning. We demonstrate multiphoton human tissue imaging at whole slide imaging speeds and with quality that matches or surpasses whole slide imaging.


A novel approach to acne treatment utilizing topical printed LED pulsed blue light
Paper 10851-11

Author(s):  Kosta Arger, CareWear Corp. (United States), et al.
Conference 10851: Photonics in Dermatology and Plastic Surgery 2019
Session 5: Therapeutics
Date and Time: 2/2/2019 2:00:00 PM

One of the barriers to the widespread use of blue light for the treatment of P.acnes has been the availability of a simple to use hands free portable light delivery system which conforms to the tissue surface and delivers clinically effective dosage without impairing vision and providing a hands-free wearable light delivery system. Our team focused on the development of a printed micro LED flexible substrate to provide 450 nm and red 632 nm pulsed light in a flexible skin adhering re-useable light patch, powered by a small Bluetooth enabled controller. Progress on ongoing clinical trials will be reported.


MFLI-FRET as an analytical tool to monitor drug distribution and penetration in tumor xenografts, liver and bladder in intact, live animals
Paper 10859-12

Author(s):  Margarida Barroso, Albany Medical College (United States), et al.
Conference 10859: Visualizing and Quantifying Drug Distribution in Tissue III
Session 3: Imaging Screening Tools in Drug Development
Date and Time: 2/2/2019 2:00:00 PM

For in vivo preclinical studies, Macroscopy Fluorescent Lifetime FRET imaging (MFLI-FRET) offers a unique platform to detect the binding of near infrared labeled probes to dimeric/oligomerized receptors and their subsequent uptake into target cells in live mice. MFLI-FRET provides longitudinal quantitative measurements of target engagement of protein-drug or antibody-drug conjugates in liver, tumor and bladder in live and intact animals. MFLI-FRET is poised to become an analytical technique of choice to measure target engagement in critical organs associated with targeted drug penetration and delivery efficiency as well as drug toxicity and clearance.


Towards in vivo preclinical monitoring of multiscale vascular structure-function relationships in resistant breast cancers with an integrated diffuse and nonlinear imaging system
Paper 10871-13

Author(s):  Kavon Karrobi, Boston Univ. (United States), et al.
Conference 10871: Multimodal Biomedical Imaging XIV
Session 3: Diffuse Optics
Date and Time: 2/2/2019 2:10:00 PM

We developed a multiscale preclinical imaging technique called Diffuse and Nonlinear Imaging (DNI) that integrates Spatial Frequency Domain Imaging (SFDI) for tissue-level mapping of tumor optical properties and hemodynamics, with Multiphoton Microscopy (MPM) to image tumor microvascular architecture with cellular resolution. We performed DNI monitoring of two mammary tumor xenograft models in BALB/c athymic nude female mice, where one model is responsive to Trastuzumab (Herceptin®) (BT474) and the other is resistant (HR6). This presentation will characterize the structure-function vascular relationships with DNI across length scales within each model, and will describe differences in the multiscale vascular relationships between the models.


Multispectral endoscopy for delineation of adenoma in pituitary surgery (MAPS): a pilot study
Paper 10862-13

Author(s):  Dale J. Waterhouse, Univ. of Cambridge (United Kingdom), et al.
Conference 10862: Molecular-Guided Surgery: Molecules, Devices, and Applications V
Session 3: Imaging Systems
Date and Time: 2/2/2019 2:15:00 PM

Multispectral imaging (MSI) collects morphological (spatial) and biochemical (spectral) information from tissue, potentially allowing us to more effectively delineate disease. Here, a multispectral endoscope was developed that is capable of capturing such morphological and biochemical information during transsphenoidal surgery. Subjects due to undergo transsphenoidal surgery to resect pituitary adenoma were enrolled for experimental imaging in a pilot clinical study (MAPS). Images were captured before, during and after resection of the adenoma. Here, we present the results from these first-in-human tests, including evaluation of the image quality and classification potential of the multispectral image cubes.


Preliminary assessment of porphysome uptake in a canine prostate cancer model for targeted photothermal focal therapy
Paper 10852-8

Author(s):  Robert A. Weersink, Princess Margaret Cancer Ctr. (Canada), et al.
Conference 10852: Therapeutics and Diagnostics in Urology 2019
Session 3: Treatment II
Date and Time: 2/2/2019 2:20:00 PM

We are currently testing interstitial photothermal therapy (PTT) for treating focal prostate cancer, utilizing near-infrared laser light delivered via interstitially-placed optical fibers covering the target volume. We are investigating the use of multi-functional porphyrin-lipid nanoparticles (porphysomes) to enhance focal PTT by improving tumor delineation in several imaging modalities and by confining treatment to the tumor for improved treatment efficacy and safety. To test this approach, a canine prostate tumor model was developed using ACE-1 canine PCa cells. We demonstrate porphysome localization within the canine prostate tumor using MR-PET, and in vivo fluorescence imaging and enhanced energy deposition during PTT.


Broadband diffuse optical imaging of tamoxifen-induced changes in breast composition and metabolism
Paper 10856-11

Author(s):  Thomas D. O'Sullivan, Univ. of Notre Dame (United States), et al.
Conference 10856: Diseases in the Breast and Reproductive System V
Session 3: Optimizing Cancer Treatment
Date and Time: 2/2/2019 2:20:00 PM

Several studies have demonstrated that hormone-blocking therapies are more effective at reducing breast cancer risk in women who exhibit >10% reduction in mammographic density compared to women who had little or no density change. This data suggests that breast density is a predictor of tamoxifen effectiveness, and that imaging biomarkers could be used as a surrogate endpoint for response to treatment. The goal of this prospective study was to assess whether diffuse optical spectroscopic imaging can measure the changes in breast composition and density under adjuvant tamoxifen treatment for breast cancer.


Optimizing the antimicrobial efficacy of pulsed 450-nm light on Propionibacterium acnes through correlation with fluorescence spectroscopy
Paper 10851-12

Author(s):  Chukuka Enwemeka, San Diego State Univ. (United States), et al.
Conference 10851: Photonics in Dermatology and Plastic Surgery 2019
Session 5: Therapeutics
Date and Time: 2/2/2019 2:20:00 PM

The dosage and treatment schedules using blue light therapy in the treatment of P.acnes have not been optimized often leading to less than satisfactory results and patient compliance. Current protocols involve irradiation with continuous wave blue light at different time intervals and with different irradiance and fluences. Our team has been developing optimized protocols using pulsed blue light with a novel wearable flexible printed LED substrate to suppress P.acnes bacterial growth. We will present optimal optical parameters and treatment schedules based on our bench top research.


Optical fiber-based sensing method for nanoparticles detection through back-scattering analysis
Paper 10872-13

Author(s):  Joana S. Paiva, INESC TEC (Portugal), et al.
Conference 10872: Optical Fibers and Sensors for Medical Diagnostics and Treatment Applications XIX
Session 3: Sensors Detectors and Treatment Tools III
Date and Time: 2/2/2019 2:20:00 PM

Considering the growing importance of nanotechnologies, the relevance of suitable nanoparticles type detection/identification methods has been enhanced. In fact, the physiological responses associated to their exposure are poorly understood. Additionally, there is a myriad of extracellular nanovesicles present in physiological fluids with high potential as cancer biomarkers. We propose a sensing technique to detect the presence of 100 nm synthetic nanoparticles in distilled water versus "blank solutions" (water only) through an optical fiber tip able to collect laser back-scattered signals. Using a single-attribute derived from such signal, this method could led to the development of a novel bio-nanoparticles detection system.


In vivo serial assessment of targeted theranostic PPAR gamma delivery for acute anti-inflammatory effects on high-risk plaques using intravascular OCT-NIRF structural-molecular imaging
Paper 10855-13

Author(s):  Joon Woo Song, Korea Univ. (Korea, Republic of), et al.
Conference 10855: Diagnostic and Therapeutic Applications of Light in Cardiology 2019
Session 3: Multimodal Imaging
Date and Time: 2/2/2019 2:20:00 PM

We developed novel theranostic agents enabling macrophage mannose receptor-targeted PPARγ (Lobeglitazone; Lobe) delivery for high-risk atherosclerotic plaque imaging and treatment. The theranostic agents showed a high affinity to macrophage foam cells, suppressed inflammatory cytokine and enhanced cholesterol efflux. We performed an in vivo study using rabbit aortae. At baseline, strong NIRF signals were clearly detected in the OCT-delineated plaques. Intriguingly, a week after the theranostic agent administration, the NIRF signals notably decreased as compared to the baseline. In accordance with in vivo imaging findings, ex vivo NIRF signals on fluorescence reflectance imaging and macrophage areas on immunostainings within plaques significantly decreased.


Application of stimulated Raman scattering for measurement of intracellular drug distribution
Paper 10859-13

Author(s):  Valerie Brunton, The Univ. of Edinburgh (United Kingdom), et al.
Conference 10859: Visualizing and Quantifying Drug Distribution in Tissue III
Session 3: Imaging Screening Tools in Drug Development
Date and Time: 2/2/2019 2:20:00 PM

Stimulated Raman scattering (SRS) microscopy in tandem with bioorthogonal Raman labelling strategies has emerged as a powerful means to visualise intracellular uptake of drugs and small-molecules. We have developed novel, highly Raman active spectroscopically bioorthogonal labels, for the sensitive and specific intracellular visualisation of small-molecules. An iterative strategy of Raman-label design and validation identified minimally perturbative bis(alkyne) labels with approximately 60-fold increase in Raman scattering activity, compared to the mono-alkynes previously used. Combining SRS microscopy with this biorthogonal Raman labelling approach enabled direct visualisation of drug uptake to be correlated with markers of cell cycle status, and mapped across intracellular structures using multi-modal imaging platforms.


Optomechanical design and manufacturing techniques for compact multimodal endoscopes
Paper 10854-16

Author(s):  David Vega, The Univ. of Arizona (United States), et al.
Conference 10854: Endoscopic Microscopy XIV
Session 3: Multimodality Imaging
Date and Time: 2/2/2019 2:30:00 PM

Multimodal optical endoscopes are complex and difficult to miniaturize. Few designs have been explained in enough detail to utilize this knowledge. We present our approach to the design and manufacturing of an endoscope that encapsulates OCM, MPM and Navigation imaging. Two optical paths are enabled through the use of dichroics. The optics are aligned by stacking them in the distal ferrule. A piezo tube is used to scan the FOV and 3D printed parts have been designed to accommodate the design needs such as positioning, handling and cleaning of parts. We will provide some of the techniques to simplify manufacturing.


comparison of fluorescence guidance systems for ICG & IRDye800 imaging
Paper 10862-15

Author(s):  Jason R. Gunn, Thayer School of Engineering at Dartmouth (United States), et al.
Conference 10862: Molecular-Guided Surgery: Molecules, Devices, and Applications V
Session 3: Imaging Systems
Date and Time: 2/2/2019 2:45:00 PM

Fluorescence guidance systems are used for different indications, and the relevant range of concentrations and the relevant dye used varies considerably for human clinical trials. Most systems are designed for high concentration ICG imaging, where 0.1 mg/kg is injected IV and perfusion is imaged, yet other applications such as delayed uptake (or second temporal window) ICG imaging can have tissue concentrations an order of magnitude or more below this. Additionally, IRDye800 is used in both antibody imaging and small protein imaging in clinical trials, but injected doses vary from therapeutic to microdose levels.


Characterization of individual cell motion in human skin capillaries by noninvasive reflectance confocal video microscopy
Paper 10877-11

Author(s):  Inga Saknite, Vanderbilt Univ. Medical Ctr. (United States), et al.
Conference 10877: Dynamics and Fluctuations in Biomedical Photonics XVI
Session 4: Tissue and Cell Dynamics
Date and Time: 2/2/2019 2:50:00 PM

In this study, we explore the feasibility to noninvasively characterize individual cell motion in the postcapillary vessels of human skin. Our preliminary data of ten healthy volunteers show that the following dynamic parameters can be extracted: blood flow velocity, number of adherent leukocytes, and number and diameter of vessels. Moreover, we show the variation in the blood flow velocity within the same vessel over time, between nearby vessels and between different body sites.


An automated parasite infection diagnostic system via open-source microscopy and deep learning
Paper 10869-16

Author(s):  Yaning Li, Univ. of Science and Technology of China (China), et al.
Conference 10869: Optics and Biophotonics in Low-Resource Settings V
Session 3: Machine Learning I
Date and Time: 2/2/2019 2:50:00 PM

We report a cost-effective, automated parasite diagnostic system that does not require special sample preparation or a trained user. Fresh fecal samples from livestock were prepared using the McMaster flotation method and imaged, followed by automatic segmentation and analysis using a convolutional neural network (CNN). Simple post-processing of the CNN output yields both egg species and egg counts. The system was validated by comparing accuracy with hand-counts by a trained operator, with excellent performance. The system was further used to image drug response over time in a single animal, showing residual disease due to drug resistance after 2 weeks.


Elasticity measurement by strain-photoacoustic imaging: theoretical derivation and validation in live animals
Paper 10880-14

Author(s):  Guan Xu, Univ. of Michigan (United States), et al.
Conference 10880: Optical Elastography and Tissue Biomechanics VI
Session 4: Computation and Modeling
Date and Time: 2/2/2019 3:00:00 PM

The uncertainty of stress in deep tissue has been a longstanding challenge to the measurement of elasticity. We recently found that the collapsing of the vasculature is a function of external stress exerted on a tissue volume. Therefore, strain-photoacoustic correlation could be an alternative to the strain-stress correlation for elasticity measurement. We examine this hypothesis using rabbit ear and a rat model of intestinal fibrosis in vivo. The experiment results agreed with the microelastometer measurements of later harvested tissues ex vivo that the stiffness of fibrotic group increases by approximately twice (p<0.05) compared to that of the control group.


Functional imaging with light and sound including microcirculation
Paper 10888-13

Author(s):  Martin J. Leahy, National Univ. of Ireland, Galway (Ireland), et al.
Conference 10888: Biophysics, Biology and Biophotonics IV: the Crossroads
Session 3: Quantitative Spectroscopy and Optical Coherence Microscopy
Date and Time: 2/2/2019 3:05:00 PM

Microcirculation provides key functions including nutrition, waste disposal, immune related transport, thermoregulation and others. This paper will provide an overview of methods, including our own, to image the microcirculation in animals and humans. It will further explore the extraction and use of sub-voxel data for fundamental biological discovery and medical diagnosis.


Combining Raman spectroscopy and photodynamic therapy for optical cancer theranostics
Paper 10860-9

Author(s):  Conor C. Horgan, Imperial College London (United Kingdom), et al.
Conference 10860: Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXVIII
Session 4: Photodynamic Therapy IV
Date and Time: 2/2/2019 3:30:00 PM

Theranostic approaches to cancer offer the possibility of individually-tailored treatments, though development of theranostic nanoparticles to achieve this is challenging. Here we demonstrate an alternative nanoparticle-free theranostic approach that circumvents many of the difficulties currently hindering clinical translation. Through the use of a multimodal optical probe, we translate the theranostic burden from complex nanoparticles to an external spectroscopic device, alleviating many of the constraints imposed on existing theranostic systems. Using this platform, we demonstrate that the combination of Raman spectroscopy and photodynamic therapy for optical theranostics enables nanoparticle-free cancer detection, diagnosis, and treatment in real-time using a single optical system.


Fat loss by red and near infrared LED phototherapy
Paper 10861-11

Author(s):  Sungkyoo Lim, Dankook Univ. (Korea, Republic of), et al.
Conference 10861: Mechanisms of Photobiomodulation Therapy XIV
Session 4: PBM Innovation and Commercialization
Date and Time: 2/2/2019 3:30:00 PM

Photobiomodulation using light from red and near infrared LEDs or Lasers have been reported effective as noninvasive methods for fat loss. A total of 50 subjects were randomly divided into test groups and control groups for abdominal fat reduction clinical trial using red and near infrared LED phototherapy devices. Red and near infrared light with irradiance of 10 mW/cm2 were irradiated over the abdominal area to the test group for 30 minutes at least 6 times a week followed by 3 times of 30 minutes of aerobic exercise a week for 4 weeks. Control group used sham devices for 30 minutes at least 6 times a week and followed by 3 times of 30 minutes of aerobic exercise a week for 4 weeks. It was shown that red and near infrared LED phototherapy combined with aerobic exercise was effective and safe for abdominal fat loss without any side effects.


Hyperspectral imaging for tumor detection in the resection surface of fresh lumpectomy specimens
Paper 10856-13

Author(s):  Esther Kho, The Netherlands Cancer Institute (Netherlands), et al.
Conference 10856: Diseases in the Breast and Reproductive System V
Session 4: Breast Cancer Surgery Technologies
Date and Time: 2/2/2019 3:30:00 PM

Real-time intra-operative resection margin assessment during breast-conserving surgery is important to prevent incomplete tumor removal. We test the feasibility of hyperspectral imaging for margin assessment of fresh lumpectomy specimens. To ensure hyperspectral images (900-1700 nm) of the entire resection surface, the specimens were imaged from six different sides. By using a SVM classification algorithm, we predicted tumor positive margins, which we compared to histopathological margin assessment. The preliminary results on the first six specimens are promising: data acquisition and analysis was fast and hyperspectral imaging was able to find 12 out of 13 positive resection sides.


Non-invasive label free Raster Scanning Optoacoustic Mesoscopy (RSOM) for imaging of skin inflammatory conditions
Paper 10851-14

Author(s):  Dinish U.S., Singapore Bioimaging Consortium (Singapore), et al.
Conference 10851: Photonics in Dermatology and Plastic Surgery 2019
Session 6: Skin Characterization/Biological Response
Date and Time: 2/2/2019 3:30:00 PM

Eczema or dermatitis, the most common inflammatory skin disease, is estimated to have affected ~245 million people worldwide based on a recent statistics. Although there may be various disease scoring systems to reflect the extent and disease severity of such chronic inflammatory skin disorders, they do not reflect the structural characteristics of the skin such as morphology, vascular architecture and changes in epidermis thickness. They are also subjected to much inter and intra-assessor variability. One of the salient features of inflammatory skin diseases is the vascular remodeling brought about by the imbalance between pro- and anti-angiogenic mediators under conditions of chronic inflammation, resulting in either vessel growth or recession. Non-invasive imaging techniques for assessing this change in skin vascular structures could potentially serve as objective indicators to characterize its severity that can help in developing an effective treatment procedure. Herein, for the first time, we present the preliminary results from an ongoing clinical study at Singapore National Skin Center, using non-invasive raster scanning optoacoustic mesoscopy (RSOM) imaging approach, which can combine the deep tissue interrogation of ultrasound and high contrast of optical techniques. Using RSOM imaging, we could objectively characterize the severity of eczema by visualizing the skin morphology and vascular pattern changes in the dermis and sub-dermis of patients enabling a quantification of inflammation in a label free manner.


Monitoring patients with oral premalignant lesions using noninvasive autofluorescence imaging
Paper 10853-15

Author(s):  Katelin D. Cherry, Rice Univ. (United States), et al.
Conference 10853: Optical Imaging, Therapeutics, and Advanced Technology in Head and Neck Surgery and Otolaryngology 2019
Session 4: Concepts in Optical Imaging for Early Detection Of Head and Neck Malignancies
Date and Time: 2/2/2019 3:40:00 PM

Patients with oral potentially malignant disorders (OPMD) must undergo regular clinical surveillance to ensure that any progression to malignancy is detected promptly. The sensitivity and specificity of clinical impression are limited, and many patients undergo frequent invasive biopsies. Widefield autofluorescence imaging (AFI) is a non-invasive optical modality that can assist clinicians in detecting early cancers and high grade dysplasia. We conducted a multi-year longitudinal study to image OPMD patients. AFI images were quantified using an automated algorithm and compared with clinical impression and histopathology, when available, to evaluate which modalities are most useful in predicting clinical outcome.


Tolerating uncertainty: photodynamic therapy planning with optical property variation
Paper 10860-10

Author(s):  Abdul-Amir Yassine, Univ. of Toronto (Canada), et al.
Conference 10860: Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXVIII
Session 4: Photodynamic Therapy IV
Date and Time: 2/2/2019 3:50:00 PM

Treatment planning is of utmost importance in interstitial photodynamic therapy, as it predicts the required light delivery to the target volume in the upcoming treatment. However, planning remains a major challenge due to uncertainties such as the tissue optical properties and the concentration of the photosensitizer and oxygen. Any small difference in these parameters from the assumed values during planning can significantly affect the outcome of the actual treatment. This work introduces PDT-SPACE, a PDT light source power allocation using convex optimization engine to minimize damage to organs-at-risk with robustness against variation in tissue optical properties.


Non-contact imaging of breast surface for breast surgical planning
Paper 10856-14

Author(s):  Olivia Tong, Univ. of Western Ontario (Canada), et al.
Conference 10856: Diseases in the Breast and Reproductive System V
Session 4: Breast Cancer Surgery Technologies
Date and Time: 2/2/2019 3:50:00 PM

Objective and accurate surface measurements of the human breast are important for surgical planning. The aim of this work was to develop a non-contact imaging system that can provide 3D information of a breast surface from patients in the same position as during surgery. Two structured-light surface scanners were combined using separate colour optical filters to minimize cross-talk between scanners. Our system performed better than currently available commercial systems and a feasibility study on patients is planned.


Low-cost, smartphone confocal microscope
Paper 10870-16

Author(s):  DongKyun Kang, College of Optical Sciences, The Univ. of Arizona (United States), et al.
Conference 10870: Design and Quality for Biomedical Technologies XII
Session 4: Mobile, Portable, and Implantable Devices
Date and Time: 2/2/2019 3:50:00 PM

We have recently developed a low-cost smartphone confocal microscope that does not require any beam scanning devices and high-bandwidth data acquisition systems. The smartphone confocal microscope uses the slit confocal aperture, broadband LED, and gratings to generate two-dimensional confocal images on a smartphone camera. The material cost for the smartphone confocal microscope was $4,200. The smartphone confocal microscope had lateral resolution of 2 µm and axial resolution of 5 µm. With only 15 µW light power illuminating the tissue, the smartphone confocal microscope was able to visualize cellular details of the human skin in vivo in near real time (4.3 frames/sec).


Designing a unique photobiomodulation treatment protocol by assessing efficient photonic and magnetic emission parameters on an Alzheimer’s disease animal model
Paper 10861-12

Author(s):  Laura Auboyer, REGEnLIFE (France), et al.
Conference 10861: Mechanisms of Photobiomodulation Therapy XIV
Session 4: PBM Innovation and Commercialization
Date and Time: 2/2/2019 3:55:00 PM

REGEnLIFE is a company developing cutting-edge therapy for neurodegenerative disorders. We have designed a medical technology relying on photobiomodulation properties and defined a unique protocol for our neurophotonic treatment. Our RGn530 device, combining photonic and magnetic emissions, has shown significant and valuable results in preclinical studies performed on an Alzheimer’s disease animal model. Treatment was tested with different parameters and a total reversal of deficits was obtained, therefore displaying a promising therapeutic efficacy for neurodegenerative disorders.


Nondestructive anatomic 3D pathology with open-top light-sheet microscopy for precision medicine
Paper 10859-15

Author(s):  Jonathan T. C. Liu, Univ. of Washington (United States), et al.
Conference 10859: Visualizing and Quantifying Drug Distribution in Tissue III
Session 4: Advanced Methods in Drug Detection and Imaging
Date and Time: 2/2/2019 4:00:00 PM

We have developed an “open-top” light-sheet (OTLS) microscopy platform for rapid slide-free 3D pathology of surgical and biopsy specimens. Our most-recent efforts have focused on optimizing a suite of technologies to demonstrate the feasibility of 3D OTLS microscopy to visualize structural and molecular biomarkers within large numbers of core-needle biopsies in toto, and ultimately to better predict patient outcomes (indolent vs. aggressive disease).


A 27-band snapshot hyperspectral imaging system for label-free tumor detection during image-guided surgery
Paper 10890-16

Author(s):  Steven M. Blair, Univ. of Illinois (United States), et al.
Conference 10890: Label-free Biomedical Imaging and Sensing (LBIS) 2019
Session 3: Spectroscopy and Scattering I
Date and Time: 2/2/2019 4:00:00 PM

Label-free image guided surgery permits surgeons to discriminate between cancerous and noncancerous tissue based on intrinsic spectral differences. Unfortunately, the state-of-the-art hyperspectral imaging systems that are required suffer issues with image resolution, frame rate, and co-registration error that limit application in the operating room. As a solution, we have monolithically integrated a stacked photodiode image sensor with pixelated interference filters to produce a single-chip snapshot hyperspectral imaging system that provides 27 spectral bands from ~450 nm to ~750 nm. This imaging system has been successfully used in preclinical trials to differentiate between cancerous and noncancerous tissue and between cancer types.


Multimodal imaging system for improved evaluation of oral premalignant lesions: a pilot study
Paper 10853-16

Author(s):  Eric C. Yang, Rice Univ., Baylor College of Medicine (United States), et al.
Conference 10853: Optical Imaging, Therapeutics, and Advanced Technology in Head and Neck Surgery and Otolaryngology 2019
Session 4: Concepts in Optical Imaging for Early Detection Of Head and Neck Malignancies
Date and Time: 2/2/2019 4:00:00 PM

Management of oral premalignant lesions (OPLs) is challenging; clinicians must decide whether an OPL should be biopsied, and if so, where to biopsy. We previously developed a multimodal imaging system (MMIS) which combines autofluorescence imaging (AFI) and high-resolution microendoscopy (HRME) to evaluate OPLs. We are conducting a pilot study in which a head and neck surgeon utilizes the MMIS to aid OPL evaluation. At present, we have acquired 14 biopsies, including five triggered by MMIS suspicion alone, from 43 patient visits. Of these five, four were moderate dysplasia or worse, suggesting that the MMIS could improve OPL management.


Esophageal OCT using endoscope-coupled paddle probe
Paper 10854-19

Author(s):  Yang Zhao, Duke Univ. (United States), et al.
Conference 10854: Endoscopic Microscopy XIV
Session 4: Advances in E-OCT
Date and Time: 2/2/2019 4:00:00 PM

We present an OCT probe implemented as a paddle attached to an upper GI endoscope. This approach allows visual navigation to regions of interest in the esophagus. The probe housing and flexible cuff were 3D printed. The optical probe was a rotating fiber-optic design, consisting of a gradient-index lens and prism on the distal end, wound steel torque coil, a polymer sheath, and a fiber-optic rotary junction. The OCT system was a 1310 nm spectral domain configuration with custom spectrometer operating at 20,000 A-lines per second.


An assessment of OCT plus micro-elastography for detection of close tumor margins following breast-conserving surgery
Paper 10856-15

Author(s):  Kelsey M. Kennedy, BriteLab, Inc. (Australia), et al.
Conference 10856: Diseases in the Breast and Reproductive System V
Session 4: Breast Cancer Surgery Technologies
Date and Time: 2/2/2019 4:10:00 PM

We present results from a >70-patient study to determine the sensitivity and specificity of OCT versus OCT plus micro-elastography for detecting cancer within 0.75 mm of the margin in fresh, intact specimens from patients undergoing breast-conserving surgery. We deployed a portable micro-elastography system capable of rapid, 3D imaging of the microstructure and stiffness of whole margins (46x46 mm). A pathologist determined tissue types present within each scan based on co-registered histology. Recruitment for the study is complete, and a blinded reader analysis is being performed by two surgeons, a pathologist, a radiologist, and an engineer.


In vivo Raman spectroscopy: monitoring cancer progression post carcinogen withdrawal
Paper 10853-17

Author(s):  C. Murali Krishna, Advanced Ctr. for Treatment, Research & Education in Cancer (India), et al.
Conference 10853: Optical Imaging, Therapeutics, and Advanced Technology in Head and Neck Surgery and Otolaryngology 2019
Session 4: Concepts in Optical Imaging for Early Detection Of Head and Neck Malignancies
Date and Time: 2/2/2019 4:20:00 PM

Studies investigating relationship between tobacco withdrawal/discontinuation and cancer-progression-risk are usually retrospective. In this study Hamster buccal pouch model which shows tumor development in 14 weeks of carcinogen-(DMBA)-application, was employed (n=20) to investigate cancer-progression after 8-weeks of DMBA-application and monitored by in vivo Raman spectroscopy (RS). For DMBA painting discontinued after 8 weeks but spectra acquired after 14 weeks, 28% spectra showed cancer-progression while for continuous 14-week application, 65% spectra showed tumor attributes. Findings can be extrapolated to tobacco habitués to suggest reduced risk of cancer progression on quitting primary consumption of tobacco


Transnasal introduction catheter, a new platform for imaging and biopsying the gastrointestinal (GI) tract
Paper 10854-20

Author(s):  Hamid Farrokhi, Wellman Ctr. for Photomedicine (United States), et al.
Conference 10854: Endoscopic Microscopy XIV
Session 4: Advances in E-OCT
Date and Time: 2/2/2019 4:20:00 PM

Upper endoscopy is a standard technique for imaging, sampling, and treating gastrointestinal tissue, frequently requiring the subjects be consciously sedated. Endoscopy is further problematic for young children (aged 0-24 months) who sometimes need to be anesthetized. To address this need, we have developed a double lumen 6.5 Fr transnasal introduction catheter (TNIC), with a liquid-metal filled balloon at the distal tip. After proper positioning, OCT-guided instruments for imaging and biopsy can be inserted through the main lumen of the TNIC. To test the feasibility of TNIC, we conducted a clinical study in 4 unsedated normal volunteers. Results showed detailed OCT endomicroscopy images.


Towards detection of positive resection margins with diffuse reflectance spectroscopy during breast conserving surgery
Paper 10856-16

Author(s):  Lisanne L. de Boer, The Netherlands Cancer Institute (Netherlands), et al.
Conference 10856: Diseases in the Breast and Reproductive System V
Session 4: Breast Cancer Surgery Technologies
Date and Time: 2/2/2019 4:30:00 PM

In this study Diffuse Reflectance Spectroscopy (DRS) is investigated for the discrimination of tumor tissue from healthy tissue in breast surgery resection specimens. With a custom made grid, DRS measurements were obtained in 71 ex vivo specimens and classified with a support vector machine based algorithm. Pure measurement locations (>95% one tissue type) were classified as fat, connective or tumor tissue with high accuracies. Locations that consisted of a mixture of tissue types were more challenging to classify. Also, with an increasing amount of tumor in the measurement volume, detection rate increased.


Optical mapping of heart rhythm with voltage sensitive fluorescence dye in WT and FHF2KO hearts
Paper 10855-19

Author(s):  Ernest W. Chang, NYU Langone Medical Ctr. (United States), et al.
Conference 10855: Diagnostic and Therapeutic Applications of Light in Cardiology 2019
Session 4: Spectroscopy and Optical Mapping
Date and Time: 2/2/2019 4:30:00 PM

Ability to image murine cardiac conduction system with voltage gated fluorescence dyes can be an important modality to simulate pathologies and monitor treatment outcomes. Here we demonstrate a genetically engineered mouse heart and our ability to capture cardiac conduction system with a voltage gated fluorescence dye (Di-4-ANEPPS).


Multiplexed paper-based assay for C-Reactive Protein (CRP) quantification using machine learning
Paper 10869-19

Author(s):  Zachary S. Ballard, Univ. of California, Los Angeles (United States), et al.
Conference 10869: Optics and Biophotonics in Low-Resource Settings V
Session 4: Machine Learning II
Date and Time: 2/2/2019 4:40:00 PM

We present a point-of-care computational sensing platform for the quantification of C-reactive protein (CRP), an important biomarker for inflammation and cardiovascular health. Our vertical flow assay is created by stacking various functional paper layers within a 3-D printed cartridge, and contains a multiplexed nitro-cellulose sensing membrane fabricated using an automated liquid dispensing system. With this multiplexed, point-of-care design, we show that quantification accuracy can be improved over a large dynamic range through the implementation of neural networks and other machine learning techniques that learn the non-linear correlations between highly multiplexed signal inputs and the ground-truth biomarker concentration.


Minimally invasive trans-nasal biopsy of the small intestine
Paper 10854-21

Author(s):  David O. Otuya, Wellman Ctr. for Photomedicine, Massachusetts General Hospital (United States), et al.
Conference 10854: Endoscopic Microscopy XIV
Session 4: Advances in E-OCT
Date and Time: 2/2/2019 4:40:00 PM

Environmental enteric dysfunction (EED) is a condition of the small intestine in low- and middle-income countries associated with nutrient malabsorption and enteropathogen susceptibility. As a result, EED is believed to cause poor neurological, immunological, and physical development of children in these countries. Biopsy of the small intestine is the current diagnostic gold standard for EED, which poses a challenge because it is unavailable in low resource settings and the requirement for sedation during upper endoscopy is not conducive for infants in their first 24 months of life when EED-related stunting can be reversed. We have developed OCT image-guided trans-nasal cryobiopsy device that requires no sedation to address this challenge.


Characterization of laser-induced retinal lesions using convolutional neural networks
Paper 10876-19

Author(s):  Mark A. Keppler, Texas A&M Univ. (United States), et al.
Conference 10876: Optical Interactions with Tissue and Cells XXX
Session 5: Cellular Biomolecular Response
Date and Time: 2/2/2019 4:50:00 PM

While the risk factor for retinal damage is increasing due to inexpensive consumer grade and high-power laser systems, retinal lesion discrimination training for eye care providers has not changed significantly. Over the last two years the Air Force Research Laboratory has assembled the largest known database of laser lesions. A deep convolutional neural network was trained on image modalities commonly found in clinical practice from including fundus, fundus autofluorescence (FAF), and optical coherence tomography (OCT). The resulting network can characterize retinal lesions by considering laser power, wavelength, duration of exposure and time since exposure.


Clinical-grade light-enhanced transesophageal echocardiography
Paper 10855-20

Author(s):  Li Li, Massachusetts General Hospital (United States), et al.
Conference 10855: Diagnostic and Therapeutic Applications of Light in Cardiology 2019
Session 4: Spectroscopy and Optical Mapping
Date and Time: 2/2/2019 4:50:00 PM

Transesophageal Echocardiography (TEE) has become an indispensable tool for diagnosing cardiovascular malfunction, guiding intervention and assessing hemodynamics. However, it still suffers from poor tissue characterization is not capable of assessing oxygen metabolism due to its sole use of acoustic contrast. We have developed light-enhanced transesophageal echocardiography (leTEE) to address the deficiency. By incorporating photoacoustic measurements into TEE, leTEE can provide better evaluation of tissue composition and direct determination of blood oxygenation. We will present our development of a clinical-grade system, results on ex-vivo myocardial characterization and in-vivo monitoring of mixed venous oxygenation in human-sized swine, and recent progress towards three-dimensional imaging.


Combined reflectance confocal microscopy - optical coherence tomography for detection and deep margin assessment of basal cell carcinomas: a clinical study
Paper 10871-19

Author(s):  Aditi Sahu, Memorial Sloan-Kettering Cancer Ctr. (United States), et al.
Conference 10871: Multimodal Biomedical Imaging XIV
Session 4: Deep Learning
Date and Time: 2/2/2019 5:00:00 PM

The diagnosis and treatment of basal cell carcinoma (BCC) is based on biopsy-histopathologic findings. In a clinical study on 85 lesions (both, previously biopsied, and suspicious lesions), we have evaluated a combined Reflectance confocal microscopy (RCM) - optical coherence tomography (OCT) system for non-invasive, real-time and more comprehensive diagnosis and depth assessment of BCCs in patients. Our findings demonstrate high sensitivity and specificity in diagnosis of BCCs and high correlation in OCT-predicted depth and histopathologically-measured depth, highlighting the potential utility of this device for non-invasive diagnosis and triage of BCCs in prospective clinical settings.


Label-free remote photonic sensing of blood vessels' hemodynamics and occlusion in the brain
Paper 10890-20

Author(s):  Zeev Zalevsky, Bar-Ilan Univ. (Israel), et al.
Conference 10890: Label-free Biomedical Imaging and Sensing (LBIS) 2019
Session 4: Speckle Imaging
Date and Time: 2/2/2019 5:00:00 PM

A novel photonic method for remote label free monitoring of brain activity associated with hemodynamic changes, is presented. The approach relies on observation of the secondary speckle patterns that are created by illuminating the skull using a laser beam after the back scattered light passed via special optics and digitally processed with fast CMOS camera. Nano-vibrations due to blood flow and tissue oxygenation in the brain cause the self-interference random patterns to change by affecting the light waves. By analyzing the spatial-temporal changes of the speckle pattern distribution we extract the nano-metric vibrations of the blood vessels due to the hemodynamic responses caused on subjects given different visual stimulating tasks. The experiment included visual stimulation consisting from 10 seconds of a flashing checkerboard. Each subject was examined with 16 different blocks of rest and visual stimulation. The temporal vibrations were analyzed during rest and stimulation. Furthermore, the remote approach was tested with a multi-wavelength method. This experiment was repeated 10 times and the averaged data was calculated using a magnitude-squared wavelet coherence function. The results show the ability to remotely detect brain functionality using the presented method. Furthermore, The proposed method is also inspected in its applicability to detect potential occlusions in blood arteries in the brain of the subjects as well as below at blood arteries positioned below the surface of the tissue that is being illuminated by the laser beam.


A novel multimodal optical imaging device for cervical cancer screening and diagnosis
Paper 10856-20

Author(s):  Shiri Gordon, Biop Medical Ltd. (Israel), et al.
Conference 10856: Diseases in the Breast and Reproductive System V
Session PSat: Posters-Saturday
Date and Time: 2/2/2019 5:15:00 PM

Cervical cancer is the fourth most common cancer in women worldwide. In developing countries, it is a leading cause of death. Biop Medical has developed a portable multimodal optical imaging device for early screening and detection of cervical intraepithelial neoplasia (CIN). The device is a non-invasive probe which scans the cervix area and combines information from multiple optical modalities, for in vivo, real time detection of CIN. In this paper we present sample data acquired from 18 patients using the device in an in-vivo pilot study and present preliminary results of classification into low-grade and high-grade cervical intraepithelial lesions.


Comparison of flash-lamp Er:YAG laser and diode pumped Er,La:SrF2-CaF2 laser for dental tissues interaction
Paper 10857-24

Author(s):  Tatjána Dostálová, Charles Univ. (Czech Republic), et al.
Conference 10857: Lasers in Dentistry XXV
Session PSat: Posters-Saturday
Date and Time: 2/2/2019 5:15:00 PM

Hard dental tissue removal by laser radiation is an alternative method to conventional dental drilling procedures. The most effective systems for those purposes are Erbium-family lasers generating radiation at wavelengths of around 3 μm. Disadvantage of these systems is their size. Newly developed Er,La:SrF2-CaF2 laser is also generating radiation with wavelength ~ 3 μm. This system is generating long 5 ms pulses with repetition rate 10 Hz and 54 mW interaction power. The aim of our study was investigation and comparison of those laser systems during interaction with dental tissues mainly for laser ablation and endodontic therapy.


Bone fracture healing by low level laser therapy (LLLT)
Paper 10876-35

Author(s):  Mohammad Nazrul Islam, Shaheed Suhrawardy Medical College and Hospital (Bangladesh), et al.
Conference 10876: Optical Interactions with Tissue and Cells XXX
Session PSat: Posters-Saturday
Date and Time: 2/2/2019 5:15:00 PM

'BONE FRACTURE HEALING' By LOW LEVEL LASER THERAPY ( LLLT) Background Data: Tissue healing is a complex process that involves both local and systemic responses, and the healing process of bone is much slower than that of soft tissues which is a great challenge of medical science. Theuse of Laser Therapy (LLLT) for wound /bone healing has been shown to be effective in modulating bothlocal and systemic response by enhancing- cellular & mitochondrial ion exchange, bone mineralization,nitric oxide formation, lymphatic circulation, osteoblast proliferation, effects on osteoblast gene expression, osteoclast inhibition (prevents bone mineral resorption) and by bone engraftment on synthetic materials. Objective: Laser (Semiconductor diode, Ga-Al-As, 830nm) is effective in human bone regeneration, i.e. it enhances bone fracture healing. Methods: 40 (Twenty in laser & Twenty in control group) otherwise healthy men and women with, closed appendicular bone fracture (Radius/ ulna, or Femur / Tibial shaft /Clavicle / Meta carpal /Meta-tarsal) was enrolled for fracture management by laser therapy adjunctive to regular management, and was determined by clinical and radiological findings (X-ray)/at 2nd , 3rd, 4th and 6th week post fracture. Assessment included fracture line/margins, fracture gap, external callus appearance, callus-to-cortex ratio, bridging, and radiological union as well as clinical assessment of the fracture- compliance of patient, and onwards follow-up of patients, in comparison to controlled group. Results: Early significant bone regeneration /callus formation achieved by early application of Low Level laser therapy (Ga-Al-As, 830 nm) on human fractured long (appendicular) bone. Conclusions: Treatment with 830 nm diode laser has substantially reduced the fracture healing time as well as improved the quality/quantity of callus formation of the patient, thus enhancing fracture healing. Laser biostimulative effects on bone could be a new dimension for bone regeneration which significantly reduce healing period, lessen cost of treatment, and enhance patient compliance in medical science.


Soft tissue wound healing by low level laser
Paper 10876-36

Author(s):  Mohammad Nazrul Islam, Shaheed Suhrawardy Medical College and Hospital (Bangladesh), et al.
Conference 10876: Optical Interactions with Tissue and Cells XXX
Session PSat: Posters-Saturday
Date and Time: 2/2/2019 5:15:00 PM

'SOFT TISSUE WOUND' HEALING BY LOW LEVEL LASER Background: In 1967 a few years after the first working laser was invented, Endre Mester. He took some mice, shaved the hair off their backs, divided them into two groups and gave a laser treatment with a low powered ruby laser to one group. They did not get cancer and to his surprise the hair on the treated group grew back more quickly than the untreated group. That was how "laser biostimulation" effects were discovered. (Effect of laser on hair Growth of mice (in Hungarian). Mester, E. Szende, B. and Tota, J.G. (1967). Kiserl Orvostud 19. 628-631). Purpose of the work: The effects of pulsed monochromatic light, with fixed pulsations and wavelengths, on the healing of pressure ulcers were evaluated in this prospective, randomized, controlled study. Method: A placebo-controlled, double-blind study using low energy photon therapy (LLLT) was performed in ten patients with bedsore on the back. Treatment was given three times a week for 10 weeks, using monochromatic (red) optical sources; diode 660nm (GaAl-660). The patients who were randomized to placebo treatment received sham therapy from an identical-appearing light source from the same delivery system. Results: Ten patients with bedsore were randomized to receive LLLT or placebo therapy. At the conclusion of the study, the percentage of the initial ulcer area remaining unhealed in the LLLT and placebo groups was 24.4% and 84.7%, respectively (P = 0.0008). The decrease in ulcer area (compared to baseline) observed in the LLLT and placebo groups was 193.0 mm2 and 14.7 mm2, respectively (P = 0.0002). One patient dropped out of the study, complaining of lack of treatment efficacy; he was found to be randomized to the placebo group. There were no adverse effects. Conclusions: In this placebo-controlled, double-blind study LLLT was an effective modality for the treatment of bedsore which were resistant to conventional medical management. The results are encouraging as pulsed monochromatic light increased healing rate and shortened healing time. This will positively affect the quality of life in elderly patients with pressure ulcers.


Speckle reduction in laser illuminated endoscopy using adversarial deep learning
Paper 10889-42

Author(s):  Taylor L. Bobrow, Johns Hopkins Univ. (United States), et al.
Conference 10889: High-Speed Biomedical Imaging and Spectroscopy IV
Session PSat: Posters-Saturday
Date and Time: 2/2/2019 5:15:00 PM

We demonstrate the application of adversarial deep learning to reduce speckle artifact in images acquired with coherent laser light illumination. A conditional generative adversarial network (cGAN) is trained to learn transformations between images illuminated with coherent and incoherent light sources. The network is then benchmarked against state of-the-art noise reduction methods. For validation, we perform ex-vivo, gastrointestinal porcine tissue imaging with laser light and compare to LED illumination. In addition to the benefits of using a laser source instead of a lamp, this method enables simultaneous speckle flow contrast imaging and conventional RGB imaging with a single source.


Machine learning of artificial neural networks for Raman and Infrared spectra for medical routine: an automatic approach
Paper 10889-43

Author(s):  Luís Felipe C. Carvalho, Univ. de Taubaté (Brazil), et al.
Conference 10889: High-Speed Biomedical Imaging and Spectroscopy IV
Session PSat: Posters-Saturday
Date and Time: 2/2/2019 5:15:00 PM

The field of Raman and FT-IR spectroscopy has grown greatly in the medical field, but much still needs to be done so that the techniques become part of medical and dental routines. For this study we will use oral in vivo spectra obtained from studies with Raman spectroscopy and FT-IR spectra obtained from urine samples. The methods used as pre-processing of the data will be vector normalization, by area and maximum peak intensity and multivariate analyzes such as PCA and PLSR. We also used linear discriminant analysis with cross-validation, and compared with neural network techniques such as J48, Randon Forest, and Multilayer Perceptron.


Pharmacokinetic biodistribution assessment of Phosphorescent sensor, PtG4 Oxyphor in mice for optimization of in vivo oxygenation imaging
Paper 10862-51

Author(s):  Mengyu Jia, Dartmouth College (United States), et al.
Conference 10862: Molecular-Guided Surgery: Molecules, Devices, and Applications V
Session PSat: Posters-Saturday
Date and Time: 2/2/2019 5:15:00 PM


Artery and vein differentiation in retinal optical coherence tomography angiography of macular region
Paper 10858-55

Author(s):  Taeyoon Son, Univ. of Illinois at Chicago (United States), et al.
Conference 10858: Ophthalmic Technologies XXIX
Session PSat: Posters-Saturday
Date and Time: 2/2/2019 5:15:00 PM

Differential artery-vein analysis is valuable for early detection of diabetic retinopathy (DR) and other eye diseases. As a new optical coherence tomography (OCT) imaging modality, emerging OCT angiography (OCTA) provides capillary level resolution for accurate examination of retinal vasculatures. However, differential artery-vein analysis in OCTA, particularly for macular region in which blood vessels are small, is challenging. In coordination with an automatic vessel tracking algorithm, we report here the feasibility of using near infrared OCT oximetry to guide artery-vein classification in OCTA of macular region.


Multimodal imaging for monitoring suprachoroidal injections in porcine eyes in vivo
Paper 10858-60

Author(s):  Ygal Rotenstreich, The Chaim Sheba Medical Ctr., Tel Hashomer (Israel), et al.
Conference 10858: Ophthalmic Technologies XXIX
Session PSat: Posters-Saturday
Date and Time: 2/2/2019 5:15:00 PM

Spectral domain optical coherence tomography (SD-OCT), infra-red and multicolor fundus imaging were used to monitor efficacy and safety of therapeutics into the suprachoroid of domestic pigs. Vital dyes and triamcinolone acetonide were injected into the suprachoroid using a novel minimally-invasive adjustable-depth blunt injector. Imaging analysis demonstrated that injected therapeutics covered over 80% of the posterior eye surface with no retinal detachment, hemorrhages or inflammation up to one month following injection. Multimodal imaging enables longitudinal monitoring of safety and efficacy of therapeutics delivery into the EVSC in pig eyes.


Imaging human retinal pathologies with off-axis full-field time-domain OCT
Paper 10858-66

Author(s):  Peter Koch, Medizinisches Laserzentrum Lübeck GmbH (Germany), et al.
Conference 10858: Ophthalmic Technologies XXIX
Session PSat: Posters-Saturday
Date and Time: 2/2/2019 5:15:00 PM

We present first results imaging patients with various eye diseases with an Off-Axis Full-Field Time-Domain OCT (OA-FF-TD-OCT) setup. OA-FF-TD-OCT is a promising novel technology for a simple and robust retina imaging system. It allows the design of a handheld OCT and opens the path towards a home care OCT device for AMD patients. First measurements showed that the majority of patients can use the clinical device autonomously. Although inferior compared to FD OCT systems the image quality is sufficient to determine the relevant disease marker of wet AMD.


Macular pigment reflectometry: development and evaluation of a novel clinical device for rapid objective assessment of the macular carotenoids
Paper 10858-78

Author(s):  Pinakin Davey, Western Univ. of Health Sciences (United States), et al.
Conference 10858: Ophthalmic Technologies XXIX
Session PSat: Posters-Saturday
Date and Time: 2/2/2019 5:15:00 PM

The QuantifEye-Macular Pigment Reflectometer (MPR) is a near commercial prototype developed by ZeaVision. It objectively measures lutein optical density, zeaxanthin optical density and overall macular pigment optical density (MPOD). Here we evaluate the repeatability obtained using the MPR and compare it with the current gold-standard (MPSII). The QuantifEye-MPR shows better repeatability at MPOD measurements than the MPSII. Pupillary dilation is not necessary to obtain repeatable MPOD from the QuantifEye-MPR


Optical monitoring of the spinal cord during ischemic injury
Paper 10864-17

Author(s):  David R. Busch, The Univ. of Texas Southwestern Medical Ctr. at Dallas (United States), et al.
Conference 10864: Clinical and Translational Neurophotonics 2019
Session 4: Optical Spectroscopy: Pre-Clinical II
Date and Time: 2/2/2019 5:20:00 PM

Ischemia may underlie many spinal cord injuries. We have developed a minimally invasive diffuse optical and correlation spectroscopy monitor of spinal cord hemodynamics, which may be applied throughout surgery or in acute care settings. This device has been tested in an adult pig model during systemic and local ischemia, reporting local blood flow and oxygen saturation at >0.1 Hz.


Cycloid scanning optical coherence tomography for imaging of gastrointestinal pathology
Paper 10854-23

Author(s):  Jason Zhang, Massachusetts Institute of Technology (United States), et al.
Conference 10854: Endoscopic Microscopy XIV
Session 4: Advances in E-OCT
Date and Time: 2/2/2019 5:20:00 PM

We developed a novel, side-viewing, distal 2D scanning technique that enables microscopic precision scanning over large fields for three-dimensional optical coherence tomography (3D-OCT). The scan is generated using a piezoelectrically-driven resonant scan for the fast axis and a circumferential rotary scan for the slow axis, generating a cycloid curve. Using a ~1.2 MHz swept-source VCSEL OCT system, we demonstrated imaging of 1 mm x 38 mm fields with 8.5 µm axial and 30 µm transverse resolution at 3 volumes/s. Ongoing studies aim to demonstrate higher resolution 3D-OCT for improved evaluation of upper and lower gastrointestinal pathologies.


Assessment of bacteria microencapsulation performance through bio-speckle dynamic analysis
Paper 10890-21

Author(s):  Vittorio Bianco, Istituto di Scienze Applicate e Sistemi Intelligenti "Eduardo Caianiello" (Italy), et al.
Conference 10890: Label-free Biomedical Imaging and Sensing (LBIS) 2019
Session 4: Speckle Imaging
Date and Time: 2/2/2019 5:25:00 PM

In recent years, the use of probiotics in food and health has increased enormously. Whenever food products or pharmaceutical formulations contain microencapsulated probiotics, it is crucial to quantify the effectiveness of micro-encapsulation as a microbial protection system over the time, e.g. during the shelf life of a product and during gastro-intestinal transit. Here we use bio-speckle decorrelation as a tool for the rapid assessment of microencapsulation effectiveness, suitable for applications in food science and industry. Through bio-speckle decorrelation, we quantify the shelf-time of alginate-encapsulated Lactobacillus rhamnosus and Lactobacillus plantarum probiotic bacteria and their survival rate under simulated gastro-intestinal conditions.


Paired-agent imaging of EGFR provides high sensitivity and specificity oral head and neck cancers for surgical resection
Paper 10853-21

Author(s):  Kimberley S. Samkoe, Geisel School of Medicine (United States), et al.
Conference 10853: Optical Imaging, Therapeutics, and Advanced Technology in Head and Neck Surgery and Otolaryngology 2019
Session 5: Optical and Related Imaging for Detection and Assessment of Invasive Head and Neck Cancer
Date and Time: 2/2/2019 5:40:00 PM

Single fluorescence targeting agents have been successfully used for tumor detection of head and neck cancers in pre-clinical and clinical settings; however, the arising fluorescent signal is qualitative at best and provides modest tumor-to-normal tissue contrast. Paired-agent imaging (PAI) has the potential to significantly increase sensitivity and specificity of tumor detection by quantifying receptor expression. PAI is achieved by co-administering a targeted agent (ABY-029) with a non-targeted perfusion agent (IRDye 700DX) that references the plasma delivery and leakage. It was found that PAI has significantly higher sensitivity and specificity in EGFR expressing tumors than a targeted agent alone.


Robust photometric stereo endoscopy via deep learning trained on synthetic data
Paper 10871-22

Author(s):  Faisal Mahmood, Johns Hopkins Univ. (United States), et al.
Conference 10871: Multimodal Biomedical Imaging XIV
Session 4: Deep Learning
Date and Time: 2/2/2019 6:00:00 PM

Topographic information of the colon mucosa is known to reduce lesion miss rate during conventional endoscopy. In this work, we use deep learning to estimate depth and surface topography from a photometric stereo endoscope with four alternating light sources. We developed a photometric stereo endoscopy simulator and collected synthetic data with ground truth depths. These data were used to train a deep convolutional network that fuses features from all four light sources. Our experimentation demonstrates that, when compared to monocular depth estimation, this setup can reduce the average NRMS error for depth estimation in a silicone colon phantom by 38% and in a pig colon by 31%.


Polarized light Monte Carlo simulation of cervical collagen ultrastructure
Paper 10876-23

Author(s):  Joseph Chue-Sang, Florida International Univ. (United States), et al.
Conference 10876: Optical Interactions with Tissue and Cells XXX
Session 6: Numerical Approaches Simulating Laser-Tissue Interactions and Response
Date and Time: 2/3/2019 8:00:00 AM

Polarized light microscopy and polarimetry assesses changes in cervical structure by targeting collagen. We used Mueller Matrix polarimetry to image the human cervix in-vivo to determine loss of collagen arrangement associated with later stages of pregnancy. To improve our system, we developed a Polarized Light Monte Carlo model capable of characterizing polarized light interaction with the birefringent, scattering, and absorbing medium of the cervix. We utilized this model to investigate the effect of cervical collagen arrangement of late stage in pregnancy on polarized light. we will illustrate the model framework, its validations, and provide several test cases in model cervices.


Assessing muscle tone with endoscopic PS-OCT
Paper 10854-24

Author(s):  David C. Adams, Massachusetts General Hospital (United States), et al.
Conference 10854: Endoscopic Microscopy XIV
Session 5: OCT Contrast, Resolution, Function
Date and Time: 2/3/2019 8:00:00 AM

Understanding the role of airway smooth muscle (ASM) is fundamental to forming a complete understanding of pulmonary diseases such as asthma. In this presentation we apply our recently developed technique for obtaining the corrected optic axis (OA) in endoscopic polarization-sensitive optical coherence tomography (PS-OCT) datasets to the assessment of ASM tone. By incorporating both OA and retardance measurements into our assessments, we demonstrate that we are able to obtain strong correlations between our imaging metrics and ASM tone. These results have important implications in the future research and treatment of diseases involving muscle abnormality such as asthma.


Acoustically actuated holographic microscopy for detection of nanoparticles in solution
Paper 10869-21

Author(s):  Aniruddha Ray, Univ. of California, Los Angeles (United States), et al.
Conference 10869: Optics and Biophotonics in Low-Resource Settings V
Session 5: Smartphone-Based Imaging and Sensing Technologies I
Date and Time: 2/3/2019 8:10:00 AM

We present a high-throughput method for detecting nanoparticles in solution using an acoustically actuated holographic microscope. An interdigital transducer was used to generate surface acoustic waves coupled to a thin liquid film, containing the nanoparticles on a disposable chip. The resulting standing wave causes a displacement of the fluid from the surface, creating localized liquid structures around the nanoparticles, acting as nanolenses. These nanolenses enable the detection of nano-sized particles by enhancing their optical signal, which is recorded using a field-portable and cost-effective lens-free holographic microscope. We demonstrated the success of this approach by detecting viruses, bacteria and nanoparticles.


Radio-frequency ablation monitoring through real-time, video-rate all-optical ultrasound imaging
Paper 10855-22

Author(s):  Erwin J. Alles, Univ. College London (United Kingdom), et al.
Conference 10855: Diagnostic and Therapeutic Applications of Light in Cardiology 2019
Session 5: Therapy and Monitoring
Date and Time: 2/3/2019 8:20:00 AM

Recently, an all-optical ultrasound imaging setup (employing photoacoustic ultrasound generation within a generator membrane and pulse-echo signal detection using a fibre-optic Fabry-Pérot cavity) was presented that achieved video-rate 2D images of cardiac tissue. Unlike conventional electronic ultrasound imaging probes, this all-optical ultrasound imaging setup is insensitive to electromagnetic interference, and hence well-suited to monitoring lesion delivery during radiofrequency ablation treatment. Here, we present the first real-time, video-rate all-optical ultrasound monitoring of the formation of radiofrequency ablation lesions in ex vivo tissue samples, and demonstrate the ability to track the progression of the ablation lesion.


μOCT reflectivity and texture analysis of clinically-acquired images of cystic fibrosis mucus
Paper 10854-25

Author(s):  Hui Min Leung, Massachusetts General Hospital (United States), et al.
Conference 10854: Endoscopic Microscopy XIV
Session 5: OCT Contrast, Resolution, Function
Date and Time: 2/3/2019 8:20:00 AM

The assessment of mucus rheological properties of cystic fibrosis (CF) patients who often suffer from impaired mucociliary clearance is important. As opposed to traditional in vitro measurement techniques, our recent clinical translation of an intranasal micro-optical coherence tomography (μOCT) technology provides a unique opportunity to capture the optical and microstructural properties of intact airway surface liquid (ASL) and mucus of human subjects with sub-cellular detail. Here, we present the use of μOCT reflectivity of ASL in clinically acquired μOCT videos as a proxy to their dynamic viscoelastic measures. Furthermore, texture analyses were explored to investigate if they enable effective delineation of CF mucus from non-CF.


1060 nm high definition tethered capsule OCT endomicroscopy for upper gastrointestinal tract imaging
Paper 10854-26

Author(s):  Barry Vuong, Wellman Ctr. for Photomedicine, Massachusetts General Hospital (United States), et al.
Conference 10854: Endoscopic Microscopy XIV
Session 5: OCT Contrast, Resolution, Function
Date and Time: 2/3/2019 8:40:00 AM

OCT-based tethered capsule endomicroscopy (TCE) has shown promise for upper gastrointestinal (GI) tract screening as it is capable of imaging depth-resolved microscopic morphology in unsedated patients. In this work, we demonstrate a novel design of a high lateral resolution OCT-TCE device as a 1060 nm high definition (HD) OCT. This HDOCT has a lateral resolution of ~3.6 μm over a depth range of ~ 1.6 mm. This suggest that the use of 1060 nm HDOCT may be a promising avenue for improving the accuracy of OCT-TCE for the diagnosis of upper GI diseases.


Clinical evaluation of a high resolution 3D photoacoustic scanner for the assessment of peripheral vascular disease: technical feasibility and clinical utility
Paper 10878-2

Author(s):  Nam Trung Huynh, Univ. College London (United Kingdom), et al.
Conference 10878: Photons Plus Ultrasound: Imaging and Sensing 2019
Session 1: Clinical Imaging: In Vivo, Ex Vivo, and Towards I
Date and Time: 2/3/2019 8:45:00 AM

A 3D high resolution scanner has been developed specifically for clinical use. The novel scanner architecture employing multiple interrogation beams can acquire a 3D image in less than 1 second. An initial technical validation study has been undertaken in human volunteers to determine repeatability, reproducibility and patient acceptability. Thereafter, a first-in-man clinical study aimed at assessing diagnostic accuracy in patients with peripheral vascular disease (PVD) has been completed.


Custom bile duct phantom for first-in-human multiplexed NIR fluorescence peptide imaging
Paper 10870-22

Author(s):  Yang Jiang, Univ. of Washington (United States), et al.
Conference 10870: Design and Quality for Biomedical Technologies XII
Session 5: NIR Phantoms and Phantom Design
Date and Time: 2/3/2019 8:50:00 AM

A soft, flexible synthetic human bile duct was fabricated. Due to complex structure of the biliary system, 3D printing was used for the template mold using Polyvinyl Acetate (PVA), which can be later dissolved. Cured gelatin patches with different concentrations of fluorescence dyes were placed onto the mold. Then silicone rubber with pigments to simulate visual appearance was painted in layers. After silicone curing, the phantom was placed in warm water (40-degreeC) to dissolve PVA. Two different multimodal scanning fiber endoscope systems, RGB reflectance+NIR fluorescence and 3 fluorescence (IRDye800, Cy5, and FITC)+grayscale reflectance, were used to test the phantom.


Assessment of neuropathologies with nonlinear microscopy for three-dimensional optical histology
Paper 10868-1

Author(s):  Oscar M. Carrasco-Zevallos, Massachusetts Institute of Technology (United States), et al.
Conference 10868: Advanced Biomedical and Clinical Diagnostic and Surgical Guidance Systems XVII
Session 1: Non-Cancer Applications I
Date and Time: 2/3/2019 9:00:00 AM

Formalin fixed paraffin embedded (FFPE) histology is the gold standard for histologic diagnosis, but long processing times preclude its use for intraoperative consultation during brain tumor surgery and brain biopsies. We report on nonlinear microscopy and virtual H&E histology image rendering of neuropathologies to determine feasibility for rapid intraoperative histologic analysis. Human brain tumor and normal tissue specimens from autopsies were imaged with a custom two-photon microscope and rendered in a virtual H&E histology color map in real-time. Three-dimensional virtual H&E histology images were compared to FFPE histology to assess correspondence of markers necessary for intraoperative pathology consultation.


Time-resolved fluorescence for detecting of rapidly activated transcription factor interaction with the near-infrared oligonucleotide probes in vitro and in situ
Paper 10877-17

Author(s):  Alexei A. Bogdanov, Univ. of Massachusetts Medical School (United States), et al.
Conference 10877: Dynamics and Fluctuations in Biomedical Photonics XVI
Session 5: Keynote Session
Date and Time: 2/3/2019 9:00:00 AM

Rapidly activated transcription factors (NF-kB, STAT-family, CREB/ATF and others) are critically important for regulating downstream events resulting from the pro-inflammatory signaling and cell stress, including heat shock and unfolded protein response. We developed and tested a family of transcription factor-recognizing stabilized oligonucleotide duplex-based probes (ODND) for direct detection and potential imaging of transcription factor activation in situ and in vivo. Using model systems and time-domain fluorescence lifetime (FL-TD) microscopy (FLIM) as well as macroscopic imaging measurements we determined that ODND based on interacting emitting and non-emitting FRET near-infrared fluorophore pairs reveal statistically significant changes of FL associated with the interaction of transcription factors with the probes carrying specific recognition sequences. The obtained results in vitro and in situ have strong potential in designing the strategies directed at the imaging of transcription activation machinery in common human pathologies.


Automatic pigmented lesion segmentation through a dermoscopy-guided OCT approach for early diagnosis
Paper 10851-19

Author(s):  Cristina López Sarachaga, Tecnalia (Spain), et al.
Conference 10851: Photonics in Dermatology and Plastic Surgery 2019
Session 7: Optical Coherence Tomography
Date and Time: 2/3/2019 9:00:00 AM

Early diagnosis of pigmented lesions is an unmet clinical need that would help to improve patient prognosis. The current gold standard non-invasive imaging technique during diagnosis is dermatoscopy (DD). Recently, new medical imaging techniques as Optical Coherence Tomography (OCT) have been proven on dermatology. Delineation of margins on early stages of the disease on OCT images is challenging. This work proposes combining DD and OCT images information with the goal to improve decision making during diagnosis and treatment. Image processing techniques have been applied to guide lesions delineation on OCT image with the clinical features detected on DD images.


Near-infrared fluorescence imaging using new compounds specifically targeting biliary and urinary systems in vivo.
Paper 10862-25

Author(s):  Jaepyeong Cha, Children's National Health System (United States), et al.
Conference 10862: Molecular-Guided Surgery: Molecules, Devices, and Applications V
Session 5: Clinical Translation and Clinical Applications I
Date and Time: 2/3/2019 9:15:00 AM

Accurate, real-time visualization is critical for efficient, effective and safe surgery. Although optical imaging using near-infrared (NIR) fluorescence has been used for visualization of anatomic structures and physiologic functions in open and minimally invasive surgeries, its efficacy and adoption remain suboptimal due to the lack of specificity and sensitivity. Herein, we report a novel class of compounds, which are exclusively metabolized in liver or kidney, rapidly excreted into to biliary or urinary systems, and emitted two different NIR fluorescence spectrums.


A novel ergonomic optical coherence tomography probe optimized for supine handheld angiography of young children and infants
Paper 10858-26

Author(s):  Christian Viehland, Duke Univ. (United States), et al.
Conference 10858: Ophthalmic Technologies XXIX
Session 7: Angiography and Blood Flow II
Date and Time: 2/3/2019 9:15:00 AM

We describe the development of a non-contact, handheld optical coherence tomography angiography (HH-OCTA) probe for imaging of young children and infants in the operating room. This probe uses a novel optical design that improves performance and has an ergonomic design to facilitate alignment and stabilization. Imaging was performed in 9 children and infants during exams under anesthesia. The probe used a 200 kHz OCT engine, has a motorized stage that provides +10 to -10 D refractive error correction, and weighs 700g. The HH-OCTA images provided visualization of the retinal microvasculature in both normal and pathological eyes.


Reconstructing proximal enamel lesions from multi-view optical coherence tomography
Paper 10857-3

Author(s):  Peter H. Tomlins, Queen Mary Univ. of London (United Kingdom), et al.
Conference 10857: Lasers in Dentistry XXV
Session 1: Early Caries Detection: NIR and OCT
Date and Time: 2/3/2019 9:20:00 AM

Optical coherence tomography (OCT) has previously been shown to be sensitive to early changes in tooth enamel that precedes dental caries. However, the most challenging lesions to both diagnose and treat occur between teeth, on the inter-proximal surface. Frequently found in children, these lesions are often invisible on conventional bitewing radiographs until they have progressed beyond a reversible stage. Therefore, the aim of this study was to reconstruct a three-dimensional representation of inter-proximal carious lesions from OCT data and asses their axial extent. To do this, an in vitro model was developed, comprising extracted human teeth, arranged so as to simulate a proximal interface. At the proximal site, artificial carious lesions were induced to simulate caries at different degrees of severity. Volumetric OCT volumes were acquired from multiple views of the lesion, parallel to the plane of the proximal surface. From these, the shape, depth and volume of the lesions were reconstructed. Results were compared with x-ray microtomography measurements of the same tooth specimens.


Identification of intestinal fibrosis using spectroscopic photoacoustic imaging: feasibility study in human subjects
Paper 10878-5

Author(s):  Guan Xu, Univ. of Michigan (United States), et al.
Conference 10878: Photons Plus Ultrasound: Imaging and Sensing 2019
Session 1: Clinical Imaging: In Vivo, Ex Vivo, and Towards I
Date and Time: 2/3/2019 9:30:00 AM

Identifying fibrosis against inflammation in the intestinal strictures is critical to the management of CD. In this study, we examined the feasibility of identifying intestinal fibrosis using PA imaging in human subjects. We have scanned 3 healthy subjects and 2 CD patients, including one with the diseased location at 6 cm away from the abdominal surface. Statistical significance has been observed between the PA profiles of the normal and diseased intestines. Our initial success supports that we will be able to cover at least 84% female and 92% male of CD patients using the proposed technology.


Monitoring of autonomic dysfunction for Parkinson’s disease during head-up-tilt-table test using diffuse optical tomography
Paper 10864-22

Author(s):  Zephaniah Phillips, Korea Univ. (Korea, Republic of), et al.
Conference 10864: Clinical and Translational Neurophotonics 2019
Session 5: Optical Spectroscopy: Clinical
Date and Time: 2/3/2019 9:30:00 AM

Early symptoms of Parkinson’s disease (PD) include orthostatic intolerance (OI), an autonomic dysfunction occurring with posture changes. OI can be tested using head up tilt table (HUTT) examination with blood pressure (BP) and heart rate monitoring. However, PD patients often have vascular stenosis, so BP and cerebral perfusion may not correlate well. In this study, we implemented diffuse optical tomography to monitor cerebral perfusion during HUTT in PD patients with and without OI. We saw that PD patients with OI do not show a recovery of cerebral blood volume during tilt up period, especially in the ventrolateral prefrontal cortex.


PARPi-FL - a targeted molecular fluorescent contrast agent for non-invasive diagnosis of basal cell carcinoma
Paper 10862-26

Author(s):  Manu Jain, Memorial Sloan-Kettering Cancer Ctr. (United States), et al.
Conference 10862: Molecular-Guided Surgery: Molecules, Devices, and Applications V
Session 5: Clinical Translation and Clinical Applications I
Date and Time: 2/3/2019 9:30:00 AM

Although reflectance confocal microscopy has increased sensitivity of BCC detection, specificity remains moderate (60-70%), due to poor endogenous differential contrast between tumors and normal structures. Fluorescence confocal microscopy, using PARPi-FL, a small fluorescent molecule that targets PARP1 in nuclei, may improve specificity. We demonstrated more intense PARPi-FL staining in 25/30 (83.33%) BCC compared to normal in tissue sections and its permeability through intact ex vivo human skin. PARPi-FL has acquired an IND status for oral cancer detection in vivo and may be eventually translated as a topical contrast agent on human skin in vivo for improving specificity for detecting BCCs.


Imaging subcellular structures of gastrointestinal tract with micro optical coherence tomography (µOCT)
Paper 10854-29

Author(s):  Si Chen, Nanyang Technological Univ. (Singapore), et al.
Conference 10854: Endoscopic Microscopy XIV
Session 5: OCT Contrast, Resolution, Function
Date and Time: 2/3/2019 9:40:00 AM

The capability to disclose subcellular details in situ prior to invasive biopsy or laborious histological procedures allows endoscopists to immediately make treatment strategies. We evaluated the capability of Micro-Optical Coherence Tomography (OCT) in detecting subcellular features of gastrointestinal epithelium in situ. We acquired Micro-OCT images of fresh gastrointestinal mucosa and validate the observations in Micro-OCT with corresponding histology. The results indicated that Micro-OCT is able to recognize subcellular features of gastrointestinal epithelium at the depth direction, which could aid with the diagnosis of gastrointestinal diseases in the future.


Novel Near-Infrared Nerve-Specific Fluorophores for Image-Guided Nerve Sparing Surgical Procedures
Paper 10862-27

Author(s):  Connor W. Barth, Oregon Health & Science Univ. (United States), et al.
Conference 10862: Molecular-Guided Surgery: Molecules, Devices, and Applications V
Session 5: Clinical Translation and Clinical Applications I
Date and Time: 2/3/2019 9:45:00 AM


Photovoltaic restoration of sight in age-related macular degeneration
Paper 10858-30

Author(s):  Daniel V. Palanker, Stanford Univ. (United States), et al.
Conference 10858: Ophthalmic Technologies XXIX
Session 8: Ophthalmic Therapy and Vision Restoration
Date and Time: 2/3/2019 10:15:00 AM

Photovoltaic retinal prosthesis is designed to restore sight in patients who lost central vision due to age-related macular degeneration. Subretinal photovoltaic pixels convert pulsed NIR light projected from video goggles into electric current, stimulating the nearby inner retinal neurons. This wireless design greatly reduces the surgical complexity and allows scaling the number of pixels to thousands. In rats, photovoltaic arrays with 55um pixels provided grating acuity up to a pixel pitch, corresponding to about 20/200 acuity in a human eye. In patients with geographic atrophy, implants with 100um pixels elicited retinotopically correct pattern perception with resolution matching the pixel size.


Investigation of effect of physical activity on oxygen uptake: an application of multi-wavelength optoelectronic measurement
Paper 10872-29

Author(s):  Sijung Hu, Loughborough Univ. (United Kingdom), et al.
Conference 10872: Optical Fibers and Sensors for Medical Diagnostics and Treatment Applications XIX
Session 6: Sensors Detectors and Treatment Tools VI
Date and Time: 2/3/2019 10:30:00 AM

A major function of the cardio-respiratory system is to ensure the efficient delivery of oxygen to working tissues. Investigations into cardio-respiratory phenomena such as respiratory oxygen uptake, oxygen distribution to working tissues, oxygen utilisation by skeletal muscles etc, usually rely on the measurement of oxygen consumption during various activity states. In clinical settings this evaluation involves measuring the composition of respiratory gases in expired air that is collected through a sampling line attached to a face mask and connected to a metabolic cart (Cardiopulmonary Exercise Test system), which performs the analysis. The current study investigates a relationship between opto-electronic signal components obtained from a bespoke multi-wavelength opto-electronic patch sensor (mOEPS) and oxygen uptake. 15 healthy adults (4 females and 11 males), age: 31±6.7 years and BMI: 25±3.5 kg/m2 took part in multi-stage exercise tests which consisted of cycling, walking and running. Breath-by-breath analysis of respiratory gases was performed on expired air samples collected through an oro-nasal mask (7450 Series Silicone V2™, Hans Rudolph, USA) and fed to a Cardiopulmonary Exercise Testing (CPET) system (JAEGER™ Vyntus™ CPX, Carefusion, Germany). Preliminary results show that features extracted from the AC component of photoplethysmographic signals (an indicator of blood volume changes) collected through a skin worn opto-electronic patch sensor are linearly correlated with time varied oxygen uptake patterns. These results suggest that the mOEPS has the potential to be considered as a viable low cost, and convenient proxy for a metabolic cart in investigations involving oxygen uptake.


Bioinspired flexible 3D photonic quasi-crystal implants using inverse "coffee-stain effect" for remote intraocular pressure sensing
Paper 10895-4

Author(s):  Radwanul H. Siddique, Caltech (United States), et al.
Conference 10895: Frontiers in Biological Detection: From Nanosensors to Systems XI
Session 2: Photonic Crystals
Date and Time: 2/3/2019 10:50:00 AM

We develop a nanophotonics based real-time monitoring of intraocular pressure (IOP) for glaucoma management. The highly miniaturized nanophotonic sensor implant is made of flexible 3D photonic quasi-crystal (PQC) that behave as a pressure-sensitive optical resonator and delivers IOP readings when interrogated with near-infrared light. A new fabrication process is developed using colloidal self-assembly leading to a yet undescribed PQC that combines the periodic and amorphous morphology exploiting the inverse effect of a drying coffee-stain. The PQC results in a wide angle resonance ensuring an easy and accurate remote read-out. Finally, we are in the process of demonstrating in vivo IOP monitoring of our sensor in black New Zealand rabbit.


Cost-effective screening of nutritional and genetic anemias with a portable light scattering system
Paper 10869-27

Author(s):  Zachary J. Smith, Univ. of Science and Technology of China (China), et al.
Conference 10869: Optics and Biophotonics in Low-Resource Settings V
Session 6: Point of Care Technologies
Date and Time: 2/3/2019 10:50:00 AM

Anemia affects more than ¼ of the world’s population, but current screening methods cannot separate iron deficiency anemia (IDA) from genetic anemias such as thalassemia trait (TT), preventing targeted supplementation of oral iron. Here we present a cost-effective and accurate approach to diagnose anemia and anemia type using light scattering. We can extract red cell morphology with high accuracy and use this to classify a patient into healthy, IDA, or TT. Our system achieves >98% sensitivity and specificity for diagnosing anemia, with 81% sensitivity and 86% specificity for discriminating IDA and TT, promising cheap, accurate, and efficient widespread screening.


A polymeric silicone hydrogel with adjustable characteristics for laser-assisted tissue capturing
Paper 10876-30

Author(s):  Shahrouz Taranejoo, Wellman Ctr. for Photomedicine (United States), et al.
Conference 10876: Optical Interactions with Tissue and Cells XXX
Session 7: Photothermal Interactions
Date and Time: 2/3/2019 10:50:00 AM

Most of the current laser capturing techniques rely on thermolabile polymers through a highly-invasive inefficient procedure. Here we present a type of silicone hydrogel films as a laser-capture material to harvest tissue with higher-quality characteristics. The silicone hydrogel films were synthesized, characterized, and compared in parallel to a commercial thermo-polymer that was employed to conduct the tissue capture procedure using laser irradiation onto the tissue sample. The histopathology study results demonstrated the potential of the silicone hydrogel as an appropriate replacement of conventional laser capture materials for minimally-invasive collecting of tissue samples (Both ex-vivo and in-vivo). This research was funded by Boston scientific co.


Neonatal cerebral venous saturation measurements with a noninvasive multi-wavelength fiber-coupled laser diode optoacoustic system
Paper 10878-9

Author(s):  Irene Y. Petrov, The Univ. of Texas Medical Branch (United States), et al.
Conference 10878: Photons Plus Ultrasound: Imaging and Sensing 2019
Session 2: Clinical Imaging: In Vivo, Ex Vivo, and Towards II
Date and Time: 2/3/2019 11:00:00 AM

Noninvasive cerebral venous saturation measurements provide critical information on cerebral hypoxia in neonates. We developed, built, and calibrated in vitro a compact, multi-wavelength, fiber-coupled laser-diode optoacoustic system for these measurements through open anterior and posterior fontanelles or through the skull. We measured cerebral venous saturation in neonates with different hair color and density, ethnicity, birth weight, gestational age, and clinical histories. The obtained data suggest that the normal range of cerebral venous saturation in neonates is 59%-72%. We will also present results on influence of hair color and density, ethnicity, birth weight, and gestational age on the optoacoustic signals and measurement accuracy.


PDT photo activation irradiance monitoring during a Phase I clinical study of TLD1433 in bladder cancer
Paper 10860-17

Author(s):  Lothar D. Lilge, Univ. Health Network (Canada), et al.
Conference 10860: Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXVIII
Session 6: Photodynamic Therapy VI
Date and Time: 2/3/2019 11:00:00 AM

Irradiance monitoring in the bladder during PDT is a promising tool to standardize the radiant exposure delivered to the bladder wall during light activation. The proposed irradiance system corrects the exposure time for the varying average bladder wall tissue optical properties and changes in the optical properties within the bladder void. Monitoring the irradiance can be completed throughout the treatment with little addition to the overall treatment, but overexposure of the bladder wall and treatment-related morbidity can be avoided


What is Needed for Molecular-Specific Fluorescence Guided Surgery?
Paper 10862-29

Author(s):  Brian W. Pogue, Thayer School of Engineering at Dartmouth (United States), et al.
Conference 10862: Molecular-Guided Surgery: Molecules, Devices, and Applications V
Session 6: Clinical Translation and Clinical Applications II
Date and Time: 2/3/2019 11:00:00 AM

Molecular image-guided surgery has the potential for translating the tools of molecular pathology to real-time guidance in surgery. The strengths and opportunities must be continued but are hampered by important weaknesses and threats within the field. Key issues to solve are related to the inability of macroscopic imaging tools to resolve microscopic biological disease heterogeneity and the limitations in microscopic systems matching surgery workflow, and also parsing out true molecular specific uptake from simple enhanced permeability and retention. These are very technical concerns which can likely be solved with added technical focus. Some solid steps have been demonstrated in the use of fluorescent labeling commercial antibodies and separately in microdosing studies with small molecules.


Qualitative image comparison between in vivo endoscopic optical coherence tomography and conventional histology of the healthy human oral mucosa
Paper 10857-7

Author(s):  Julia Walther, TU Dresden (Germany), et al.
Conference 10857: Lasers in Dentistry XXV
Session 2: 3D Print and CAD/CAM: OCT Soft Tissue
Date and Time: 2/3/2019 11:10:00 AM

In contrast to histological imaging that requires tissue biopsy, optical coherence tomography (OCT) offers a non-invasive way to evaluate human oral mucosa. Therefore, measurements of twenty five healthy volunteers were performed (rigid handheld system, central wavelength λ = 840 nm, spatial resolution 11.6 µm axial and 17.4 µm lateral), including ten different regions of the oral cavity, to achieve a qualitative matching of OCT scans and histological cross sections. Results showed that OCT reveals sublayers of mucosa and underlying structures, such as blood vessels and collagen fiber bundles, but does not clearly depict deeper submucosa with the used wavelength range.


Bedsore healing by cold laser therapy (LLLT)
Paper 10861-22

Author(s):  Mohammad Nazrul Islam, Shaheed Suhrawardy Medical College and Hospital (Bangladesh), et al.
Conference 10861: Mechanisms of Photobiomodulation Therapy XIV
Session 6: PBM Clinical Translation
Date and Time: 2/3/2019 11:10:00 AM

BEDSORE HEALING by Cold Laser Therapy (LLLT) Background: In 1967 a few years after the first working laser was invented, Endre Mester in Semmelweis University Budapest, Hungary wanted to find out if laser might cause cancer. He took some mice, shaved the hair off their backs, divided them into two groups and gave a laser treatment with a low powered ruby laser to one group. They did not get cancer and to his surprise the hair on the treated group grew back more quickly than the untreated group. That was how "laser biostimulation" effects were discovered. (Effect of laser on hair Growth of mice (in Hungarian). Mester, E. Szende, B. and Tota, J.G. (1967). Kiserl Orvostud 19. 628-631). Purpose of the work: The effects of pulsed monochromatic light, with fixed pulsations and wavelengths, on the healing of pressure ulcers were evaluated in this prospective, randomized, controlled study. Method: A placebo-controlled, double-blind study using low energy photon therapy (LLLT) was performed in ten patients with bedsore on the back. Treatment was given three times a week for 10 weeks, using monochromatic (red) optical sources; diode 660nm (GaAl-660). The patients who were randomized to placebo treatment received sham therapy from an identical-appearing light source from the same delivery system. Results: Ten patients with bedsore were randomized to receive LLLT or placebo therapy. At the conclusion of the study, the percentage of the initial ulcer area remaining unhealed in the LLLT and placebo groups was 24.4% and 84.7%, respectively (P = 0.0008). The decrease in ulcer area (compared to baseline) observed in the LLLT and placebo groups was 193.0 mm2 and 14.7 mm2, respectively (P = 0.0002). One patient dropped out of the study, complaining of lack of treatment efficacy; he was found to be randomized to the placebo group. There were no adverse effects. Conclusions: In this placebo-controlled, double-blind study LLLT was an effective modality for the treatment of bedsore which were resistant to conventional medical management. The results are encouraging as pulsed monochromatic light increased healing rate and shortened healing time. This will positively affect the quality of life in elderly patients with pressure ulcers. Keywords: Bedsore Healing, Soft Tissue Healing, Decubitus Ulcer, Ulcer Healing, Wound Healing, Low Level Laser, Laser Therapy.


Tumor margin detection in ex vivo breast tumor tissues using multispectral optoacoustic tomography (MSOT)
Paper 10878-10

Author(s):  Ghayathri Balasundaram, Singapore Bioimaging Consortium (Singapore), et al.
Conference 10878: Photons Plus Ultrasound: Imaging and Sensing 2019
Session 2: Clinical Imaging: In Vivo, Ex Vivo, and Towards II
Date and Time: 2/3/2019 11:15:00 AM

Tumor removal through breast conserving surgery (BCS) is challenging due to difficulties in margin delineation resulting in 20-40% chances of recurrence. Multispectral optoacoustic tomography (MSOT) was exploited in this pilot proof of concept study to assess tumor margins in freshly excised BCS specimen. Clinical pathological and histological findings were correlated with MSOT features. MSOT successfully resolved the distribution of deoxygenated haemoglobin and lipids in the specimen to a depth of ~6 mm and provided information on whether or not the margin is involved thus indicating its potential as a promising ex-vivo imaging modality to reduce local recurrence rates post BCS.


Handheld OCT-A using spectrally encoded coherence tomography and reflectometry
Paper 10858-32

Author(s):  Joseph D. Malone, Vanderbilt Univ. (United States), et al.
Conference 10858: Ophthalmic Technologies XXIX
Session 9: Spectral Imaging
Date and Time: 2/3/2019 11:15:00 AM

Optical coherence tomographic angiography (OCT-A) technologies have been primarily demonstrated on slit-lamp systems, which preclude imaging in infants, bedridden patients, or patients who are otherwise unable to be imaged upright. Current-generation OCT-A requires densely-sampled volumetric datasets for high vascular resolution imaging, but bulk motion artifacts, resulting from saccades or eye drifts, often distort anatomic features during long acquisitions. We demonstrate handheld OCT-A using spectrally encoded coherence tomography and reflectometry (SECTR). OCT and OCT-A images were motion-corrected using motion information from en face spectrally encoded reflectometry and cross-sectional OCT images. We believe our probe will enable point-of-care functional ophthalmic imaging.


Study of collagen fiber organization in human oral mucosa by polarization-sensitive optical coherence tomography
Paper 10857-8

Author(s):  Julia Walther, TU Dresden (Germany), et al.
Conference 10857: Lasers in Dentistry XXV
Session 2: 3D Print and CAD/CAM: OCT Soft Tissue
Date and Time: 2/3/2019 11:30:00 AM

In this pilot study, polarization sensitive optical coherence tomography (PS OCT) has been used for in vivo investigation and assessment of collagen fiber organization in healthy human superficial mucosa within the anterior oral cavity. We have assessed the variation of collagen fiber alignment in labial and lingual oral mucosa, with the main observation of high birefringence within the lamina propria caused by a high level of collagen organization. Results of this study represent the first step in establishing a baseline for future pathological and comparative studies of assessing stromal changes in oral connective tissue non-invasively.


Photoacoustic monitoring of blood oxygenation during neurosurgical interventions
Paper 10878-11

Author(s):  Thomas Kirchner, Deutsches Krebsforschungszentrum (Germany), et al.
Conference 10878: Photons Plus Ultrasound: Imaging and Sensing 2019
Session 2: Clinical Imaging: In Vivo, Ex Vivo, and Towards II
Date and Time: 2/3/2019 11:30:00 AM

Multispectral photoacoustic imaging has been shown to be a prime modality to monitor hemodynamics and changes in blood oxygenation (SO2). The purpose of this work was to investigate the usefulness of the technique in assessing SO2 for neurosurgical applications. To this end, we continuously imaged in vivo a porcine brain as part of an open neurosurgical intervention with a handheld photoacoustic and ultrasonic probe. During imaging we controlled the ventilation of the animal and took arterial blood gas reference measurements.


What is the prospect of transcutaneous transmission of 980nm photobiomodulation therapy light to the spinal canal?
Paper 10861-23

Author(s):  Daqing Piao, Oklahoma State Univ. (United States), et al.
Conference 10861: Mechanisms of Photobiomodulation Therapy XIV
Session 6: PBM Clinical Translation
Date and Time: 2/3/2019 11:30:00 AM

The clinical prospect of treating spinal cord injury by photobiomodulation therapy (PBMT) is unclear as the spinal dosimetry of transcutaneous laser application is unknown, yet essential for clinical recommendations. Light irradiances at 9 sites over an 8cm length along the thoracic to lumbar segment of the spinal canal were measured in 6 cadaver dogs using a flexible intra-spinal probe, under a surface irradiance of 3.14W/cm2. The skin transmits 4-12% of 980nm PBMT light. In-contact technique is ~5 times more efficient than off-contact technique. Transcutaneous transmission of photobiomodulatory irradiance to the spinal canal will benefit from contact-probe technique and skin-clearing approaches.


Thermal welding of the porcine myocardium and aorta by 1450 nm laser with parallel vital tissue fluorescence measurements
Paper 10876-33

Author(s):  Sergei G. Sokolovski, Aston Univ. (United Kingdom), et al.
Conference 10876: Optical Interactions with Tissue and Cells XXX
Session 7: Photothermal Interactions
Date and Time: 2/3/2019 11:50:00 AM

The mechanism of vascular tissue photothermal welding is well known. The myocardium LW has not attracted much attention since its low efficiency. In our research we used a CW Raman fibre laser of 1450 nm with output optical power up to 0.5 W (doses 2.5–4.5 J/cm2). This wavelength can provide better photothermal effect with deeper tissues penetration. To validate tissue vitality before and after the welding the autofluorescence measurements was performed and it reviled significant decrease in elastin, NADH and flavins fluorescence after for myocardium and less degradable effects on the aorta. The computational model of temperature gradient will be also presented.


Light-field three-dimensional confocal laser endomicroscopy for early diagnosis of upper gastrointestinal cancer
Paper 10854-34

Author(s):  Xuefang Yang, Beihang Univ. (China), et al.
Conference 10854: Endoscopic Microscopy XIV
Session 6: SEE+CLE
Date and Time: 2/3/2019 11:50:00 AM


Intraoperative photoacoustic tomography system: a breast surgical center experience
Paper 10878-13

Author(s):  Ivan Kosik, Western Univ. (Canada), et al.
Conference 10878: Photons Plus Ultrasound: Imaging and Sensing 2019
Session 2: Clinical Imaging: In Vivo, Ex Vivo, and Towards II
Date and Time: 2/3/2019 12:00:00 PM

High re-excision rates in breast conserving surgery call for a new intraoperative approach to the lumpectomy specimen evaluation problem. The unique photoacoustic imaging system, presented here, demonstrated the capability of intraoperative photoacoustic tomography (iPAT) to deliver optical sensitivity and specificity, along with over 2 cm imaging depth, in a true clinical setting. Highly specialized acoustic transducers enabled the evaluation of tumor extent, shape, morphology and position within lumpectomy specimens measuring up to 11 cm in diameter. Comparison with conventional ultrasound (US) and x-ray validated the performance of iPAT. This approach shines a light towards more effective soft tissue abnormality assessment.


NIRS measurements of muscle oximetry in the obese
Paper 10877-21

Author(s):  Andres Rodriguez, Florida International Univ. (United States), et al.
Conference 10877: Dynamics and Fluctuations in Biomedical Photonics XVI
Session 6: Functional Imaging and Spectroscopy I
Date and Time: 2/3/2019 12:10:00 PM

Obesity affects 93 million adults in the U.S. Several studies show that BMI ratio does not fully characterize the patient’s pathophysiology. Muscle metabolism may be a more useful metric in the characterization of pathologies associated to weight gain. Near Infrared Spectroscopy (NIRS) measurement of muscle oxygenation can be used to study muscle metabolism. Commercial NIRS systems fail to produce accurate results in the presence of excess adipose thicknesses (AT). We have used Monte Carlo models of light transfer to probe the optimal source-detector separation for NIRS in the obese. We will demonstrate our system validation in optical phantoms and volunteers.


Development of innovative plasmonic nanostructures for vibrational biosensing
Paper 10894-1

Author(s):  Jürgen Popp, Leibniz-Institut für Photonische Technologien e.V. (Germany), et al.
Conference 10894: Plasmonics in Biology and Medicine XVI
Session 1: Bioplasmonics Systems
Date and Time: 2/3/2019 1:20:00 PM

In bioanalysis, there is a great need for new detection methods with molecular specificity, high sensitivity and short detection times. In this context the application of plasmon enhanced vibrational spectroscopy is especially noteworthy. Here, we introduce novel surface enhanced Raman spectroscopy (SERS) and surface enhanced IR absorption (SEIRA) approaches, which allow for an ultrasensitive bio analysis like e.g. the detection of antibiotics or disease metabolites in body liquids or forbidden substances in food. Finally, slit array metamaterial concepts for the detection of analytes down to a monolayer and for chiral biosensing will be introduced.


Smartphone confocal microscopy for imaging Kaposi’s sarcoma in low-resource settings
Paper 10869-31

Author(s):  DongKyun Kang, College of Optical Sciences, The Univ. of Arizona (United States), et al.
Conference 10869: Optics and Biophotonics in Low-Resource Settings V
Session 7: Smartphone-Based Imaging and Sensing Technologies II
Date and Time: 2/3/2019 1:30:00 PM

In this paper, we present preliminary findings from a pilot study of imaging Kaposi’s sarcoma (KS)-suspected skin lesions in Uganda with a low-cost smartphone confocal microscope. We have developed a smartphone confocal microscope at a low cost (material cost = $4,200) by using all passive confocal imaging optics in conjunction with an inexpensive LED source and a smartphone camera. Confocal imaging of skin biopsy visualized cellular features of abnormal tissues, including capillaries with irregular shapes and sizes, which are likely associated with skin tumors. The preliminary results showed promises in using the smartphone confocal microscope for examining KS-suspected skin lesions.


Quantification of multiplexed fluorescence peptides in human esophagus for early cancer detection
Paper 10854-35

Author(s):  Yang Jiang, Univ. of Washington (United States), et al.
Conference 10854: Endoscopic Microscopy XIV
Session 7: Fluorescence
Date and Time: 2/3/2019 1:30:00 PM

A multimodal scanning fiber endoscope (mmSFE) is designed to image overexpressed biomarkers associated with esophageal adenocarcinoma and high-grade dysplasia (HGD), thus detecting early neoplasia. Quantification of multiplexed fluorescence images is critical, which ‘red-flags’ suspicious regions and supports diagnosis. A mmSFE with 2.4mm flexible shaft and wide-field forward-view imaging, is designed to image two near-infrared fluorescence peptides with additional reflectance channel for anatomical identification concurrently at 30Hz. In a human clinical trial, co-registered video frames were manually selected using morphological features. T/B ratios were then calculated for the fluorescence channels in selected frames to identify subjects with HGD.


Painless versus conventional photodynamic therapy for treatment of actinic keratosis: comparison of cell death and immune response in a murine model
Paper 10860-19

Author(s):  Sanjay Anand, The Cleveland Clinic (United States), et al.
Conference 10860: Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXVIII
Session 7: Photodynamic Therapy VII
Date and Time: 2/3/2019 1:40:00 PM

ALA-PDT is well-accepted treatment for actinic keratosis (AK). However, standard PDT elicits stinging pain during illumination. In a new regimen called metronomic PDT (mPDT) or painless PDT, the illumination is delivered concurrently with ALA application. We treated a murine AK model with either mPDT or PDT followed by analyses of lesion clearance and mechanistic events. Compared to PDT, mPDT treated mice showed similar lesion clearance, decreased apoptosis, autophagy and enhanced immune modulation by infiltration of neutrophils and macrophages. Preliminary data suggest that mPDT is just as effective as conventional PDT for treatment of AK, but the mechanisms may be quite different.


Tracking cellular dynamics of human skin responses to UV exposure using in vivo multimodal microscopy
Paper 10851-27

Author(s):  Giselle (Yunxian) Tian, The Univ. of British Columbia (Canada), et al.
Conference 10851: Photonics in Dermatology and Plastic Surgery 2019
Session 9: Confocal and Multiphoton Microscopy
Date and Time: 2/3/2019 1:50:00 PM

Optical live-cell microscopy has enabled key insights in cell biology research. However, studying the cellular response dynamics in human skin in vivo has been a long-standing challenge. Addressing this need, we developed a robust non-invasive method allows repeated microscopy imaging visit to the same skin micro-location with unprecedented precision. For the first time, we visualized skin cells adapt to solar UV challenges up to two weeks. This technique also enabled quantitative assessments for characterizing melanin upward migration, blood flow increase, epidermis thickness adaptation, as well as cell proliferations.


In vivo measurements of normal, keratoconic, and post crosslinked keratoconic human cornea with optical coherence elastography
Paper 10880-32

Author(s):  Matthew R. Ford, Cole Eye Institute, Cleveland Clinic (United States), et al.
Conference 10880: Optical Elastography and Tissue Biomechanics VI
Session 8: Biomechanics of the Eye
Date and Time: 2/3/2019 2:00:00 PM

Patients with keratoconus who were scheduled to undergo corneal crosslinking (CXL) were imaged with Optical Coherence Elastography (OCE) before (


Folate receptor targeted molecular imaging of lung cancer
Paper 10862-33

Author(s):  Sunil Singhal, Perelman School of Medicine (United States), et al.
Conference 10862: Molecular-Guided Surgery: Molecules, Devices, and Applications V
Session 7: Clinical Translation and Clinical Applications III
Date and Time: 2/3/2019 2:00:00 PM

Since 2011, several clinical trials in intraoperative molecular imaging of lung cancer have been performed. Most recently, a Phase II clinical trial has been initiated to test the efficacy of folate receptor targeted imaging of pulmonary adenocarcinomas. This is the largest trial to-date in lung cancer. As of August 2018, more than 65 patients have been enrolled in the study evaluating a novel near-infrared (NIR) contrast agent that targets folate receptor alpha on pulmonary tumors. This receptor is present in virtually all lung adenocarcinomas. Several of the key findings include the dye can detect tumors at 2 cm depth of penetration, it can identify synchronous lesions and it can identify cancer cells at the margins.


Spectral fluorescence lifetime imaging through fibre towards clinical translation
Paper 10854-37

Author(s):  Gareth O. S. Williams, Queen's Medical Research Institute, The Univ. of Edinburgh (United Kingdom), et al.
Conference 10854: Endoscopic Microscopy XIV
Session 7: Fluorescence
Date and Time: 2/3/2019 2:10:00 PM

The diagnosis of in vivo lung pathology is currently costly and time consuming with initial tests being inconclusive leading to lavage and extended workup. We aim to translate technologies that can perform the initial stratification of patients within minutes, at the bedside, using condition specific fluorescent probes. Challenges occur when probes cannot achieve sufficient spectral separation from tissue autofluorescence. We present an achromatic optical laser scanning microscopy system capable of recording high speed spectral fluorescence lifetime images through a clinical imaging bundle. The system has full spectral characterisation between 500-750nm and lifetime captured with an adjustable time window of 1.6-204.8ns.


Image-guided photo-mediated ultrasound therapy as a novel method for treating eye diseases
Paper 10878-16

Author(s):  Xinyi Xie, Univ. of Michigan (United States), et al.
Conference 10878: Photons Plus Ultrasound: Imaging and Sensing 2019
Session 3: Optical Sensing and Generation of Ultrasound I
Date and Time: 2/3/2019 2:15:00 PM

A novel noninvasive image-guided photo-mediated ultrasound therapy (PUT) which concurrently applies nanosecond laser pulses and millisecond ultrasound bursts to precisely and safely remove microvessels in the eye was developed recently. Integrated with a multi-modality imaging system including photoacoustic microscopy (PAM) and optical coherence tomography (OCT), the treatment procedure and therapeutic effects of PUT can be monitored and evaluated in real time. Taking advantages of the high optical contrast among biological tissues, PUT can selectively remove microvessels without causing collateral tissue damage. The efficacy and safety of PUT were evaluated via the studies on rabbit eye models.


Biophotonic nanostructured translational implants for remote intraocular pressure sensing
Paper 10891-10

Author(s):  Radwanul H. Siddique, Caltech (United States), et al.
Conference 10891: Nanoscale Imaging, Sensing, and Actuation for Biomedical Applications XVI
Session 2: Application of Nanostructured Sensors and Nanospectroscopy
Date and Time: 2/3/2019 2:20:00 PM

Millions of years of evolution in the biological world has developed its own plethora of micro- and nanoscopic structures that convey unique optical properties with multifunctionality. Understanding the physical mechanisms ruling these properties and the development process of mesoscale structures can lead to novel photonic materials, which can benefit to major societal challenges (including medical applications and self-diagnosis). Here, we have demonstrated the use of multifunctional biophotonic nanostructured membrane inspired by transparent butterfly wings for intraocular pressure (IOP) sensing in vivo. The nanostructure integration onto the IOP sensor led to a 2.5-fold improvement in optical readout angle allowing easy handheld monitoring and in a one-month in vivo study conducted in rabbits, showed a 3-fold reduction in IOP error and 12-fold reduction in tissue encapsulation and inflammation, compared to an IOP sensor without nanostructures.


Label-free, ultrafast, wide field-of-view, and localized photoacoustic microscopy of cells, animals, and humans
Paper 10889-31

Author(s):  Chulhong Kim, Pohang Univ. of Science and Technology (Korea, Republic of), et al.
Conference 10889: High-Speed Biomedical Imaging and Spectroscopy IV
Session 8: Novel High-speed Techniques II
Date and Time: 2/3/2019 3:30:00 PM

Photoacoustic microscopy (PAM) is an emerging technology that has shown the great impacts on both preclinical and clinical research. Particularly, PAM is able to provide morphological, functional, and molecular information from cells to humans. However, imaging speed and resolution of PAM are still needed to be improved for wide-spread uses in clinical and biological research studies. In this invited presentation, we introduce our recent progresses on ultrafast, agent-free, super-resolution, and wide field-of-view photoacoustic microscopy of cells, animals, and humans. Ultimately, this development will allow us to lead to new studies in various fields such as neuroscience, cancer physiopathology, and pharmacology.


Label free detection of pre-cancerous cells in vivo with a/LCI
Paper 10890-40

Author(s):  Adam Wax, Duke Univ. (United States), et al.
Conference 10890: Label-free Biomedical Imaging and Sensing (LBIS) 2019
Session 8: OCT and Interferometry
Date and Time: 2/3/2019 4:00:00 PM

Detection of pre-cancerous tissues in the clinic remains an ongoing challenge. We have developed angle-resolved low coherence interferometry (a/LCI) for assessing cell structure using light scattering and interferometry. a/LCI has been validated with in vitro measurements to measure nuclear morphology with sub-wavelength accuracy and precision. To translate this technique, a clinical a/LCI system was developed, including an endoscope compatible fiber probe. Capabilities of a/LCI will be shown with results from clinical studies to detect pre-cancer in the esophagus and cervix . Further directions to enhance clinical utility and ergonomic ease of use will also be discussed.


PhaseStain: deep learning for virtual staining of quantitative phase images
Paper 10887-32

Author(s):  Yair Rivenson, Univ. of California, Los Angeles (United States), et al.
Conference 10887: Quantitative Phase Imaging V
Session 8: QPI Algorithms and Image Processing II
Date and Time: 2/3/2019 4:20:00 PM

We demonstrate a deep learning-based framework (PhaseStain) that uses a neural network to establish a statistical transformation between quantitative phase images of thin tissue sections and brightfield images of the same samples, imaged after their histochemical staining. By employing a generative adversarial network (GAN) based training, the deep network acts as the digital equivalent of histochemical staining. We demonstrated the success of this approach using sections of human skin, kidney and liver tissue, which were virtually-stained with H&E, Jones’ stain and Masson’s Trichrome stain, respectively. This GAN-based virtual-staining approach bypasses traditional histochemical sample preparation workflow, potentially saving time and costs.


Spatially offset optical coherence tomography
Paper 10890-41

Author(s):  Kishan Dholakia, Univ. of St. Andrews (United Kingdom), et al.
Conference 10890: Label-free Biomedical Imaging and Sensing (LBIS) 2019
Session 8: OCT and Interferometry
Date and Time: 2/3/2019 4:25:00 PM

We demonstrated a simple geometry, called spatially-offset optical coherence tomography (SO-OCT), allowing singly scattered photons from depth to be retrieved whilst suppressing the presence of multiply scattered photons (speckle). Therefore, it improves signal detection to enhance the image contrast at depth in the presence of strong scattering samples. An approximately two-fold enhancement in image contrast at depths can be observed in different biological samples, such as zebrafish and krill.


Smartphone-based imaging system for individualization of PDT treatment planning for protoporphyrin IX based skin cancer treatment
Paper 10860-26

Author(s):  Alberto J. Ruiz, Thayer School of Engineering at Dartmouth (United States), et al.
Conference 10860: Optical Methods for Tumor Treatment and Detection: Mechanisms and Techniques in Photodynamic Therapy XXVIII
Session 8: Photodynamic Therapy VIII
Date and Time: 2/3/2019 4:30:00 PM

In clinical delivery of PDT, in-situ measurement of PpIX concentration is rarely done, and yet point-probe measurements have shown extreme heterogeneity exists between patients and between lesions. Direct measurements of PpIX can provide guidance in PDT and can be used to guide critical decisions about treatment time and retreatment or further skin preparation. In this work, we present a smartphone-based fluorescence imaging system to map PpIX concentration onto a 2D image for the use in PDT treatment optimization. The prototype has been produced and tested in phantoms and early human evaluation.


First-in-human trials for microdose administration of ABY-029 for fluorescence guided surgery in three tumor types: glioma, soft-tissue sarcoma and head and neck carcinomas
Paper 10862-38

Author(s):  Kimberley S. Samkoe, Geisel School of Medicine (United States), et al.
Conference 10862: Molecular-Guided Surgery: Molecules, Devices, and Applications V
Session 8: Clinical Translation and Clinical Applications IV
Date and Time: 2/3/2019 4:30:00 PM

Near-infrared (NIR) fluorescence combined with targeting epidermal growth factor receptor (EGFR) overexpression for surgical guidance in many cancers is gaining momentum. ABY-029 is an anti-EGFR Affibody molecule conjugated to IRDye 800CW that is FDA approved as an exploratory Investigational New Drug (eIND 122681) and is being investigated in a number of promising first-in-human clinical Phase 0 trials for recurrent glioma, soft-tissue sarcoma, and head and neck cancers. Here, we summarize our experience using ABY-029 for surgical resection by describing tissue contrast and correlation of ABY-029 fluorescence to EGFR tissue expression.


Triple contrast OCT imaging: combining OCT with elastography and attenuation imaging
Paper 10877-28

Author(s):  Ken Foo, Harry Perkins Institute of Medical Research (Australia), et al.
Conference 10877: Dynamics and Fluctuations in Biomedical Photonics XVI
Session 8: Clinical Imaging and Evaluation
Date and Time: 2/3/2019 4:40:00 PM

Although optical coherence tomography (OCT) is routinely used to image the eye, in more turbid tissues, additional contrast is often needed, for example to distinguish between benign fibrous tissue and tumor in breast. This contrast can be provided by optical coherence elastography (OCE) and attenuation imaging. Here, we present images from human mastectomy specimens, co-registered with histology, and assess the improvement in tissue differentiation gained by fusing these contrast mechanisms into a hybrid image. Additionally, we explore the dependence on compression of the attenuation coefficient, and report the optimal preload to apply to maximize OCT penetration depth.


Mobile phone camera-based SpO2 measurements using broadband light and colored paper filters
Paper 10869-39

Author(s):  Morris Vanegas, Northeastern Univ. (United States), et al.
Conference 10869: Optics and Biophotonics in Low-Resource Settings V
Session 8: Oximetry and Spectral Methods
Date and Time: 2/3/2019 4:40:00 PM

The mobile health field has given rise to a surge of point-of-care diagnostic attachments for mobile phones. These attachments, however, are limited in adoption in low-resource settings due to initial acquisition and subsequent maintenance cost challenges. Point-of-care devices that require no or minimum attachment can make a great impact to the accessibility of such devices in resource-poor regions. In this abstract, we report a simulation study to demonstrate the feasibility of using an ultra-low-cost color-paper filter and a mobile phone to perform broadband pulse oximetry. We run a series of GPU-based Monte Carlo simulations using a previously segmented 7T MRI scan of a finger 3D model and estimate SpO2 using the simulated PPG signals using the Ratio of Ratios (RR) method. We evaluate the performance of different color paper filters and found that the magenta-colored filter produced the highest RR signal variations and the cyan-colored paper resulted in the largest SpO2 changes in the tested range.


Deep learning enables virtual staining of unstained tissue sections using auto-fluorescence images
Paper 10868-12

Author(s):  Yair Rivenson, Univ. of California, Los Angeles (United States), et al.
Conference 10868: Advanced Biomedical and Clinical Diagnostic and Surgical Guidance Systems XVII
Session 4: Deep Learning in Optics
Date and Time: 2/3/2019 4:50:00 PM

We demonstrate deep learning-based virtual-staining of label-free tissue sections using auto-fluorescence images. During its training process, a deep network learns the transformation of these autofluorescence images of label-free tissue sections into images that are equivalent to the brightfield images of the same samples, acquired after histochemical-staining. This framework was successfully tested using multiple types of tissue sections and stains, and the virtually-stained images were evaluated by pathologists to confirm that they very well agree with the brightfield images of chemically-stained samples. This method can save time and costs, and preserve tissues, allowing new types of molecular analysis on label-free tissue.


Photonic bio-sensor based on multiclass support vector machine with a reject option
Paper 10871-23

Author(s):  Zeev Zalevsky, Bar-Ilan Univ. (Israel), et al.
Conference 10871: Multimodal Biomedical Imaging XIV
Session PSun: Posters-Sunday
Date and Time: 2/3/2019 5:30:00 PM

In this work we explore the problem of multiclass classification where the classifier may abstain from classifying on some observation. We derivate a new surrogate loss function and a multiclass decision rule by using a reject threshold on posterior probabilities in the Bayes decision rule, known as Chow's rule. The goal of the decision rule is to minimize the value of given misprediction and rejection cost functions specified by the user. We suggest a general training algorithm by plug-in the surrogate loss in to Support Vector Machine (SVM) structure. We then test the algorithm on open data sets - free for public use multiclass data from different problems, and on a real -life problem in the photonic medical sensing field where accuracy is critical- a non-invasive way of detecting glucose level in blood to help patients with Diabetes mellitus diseases. The results will show that the value of the reject threshold has importance in determinate how many samples to reject and in the overall accuracy of prediction. As the threshold grow so does the number of samples rejected and overall accuracy, meaning that only samples with strong confidence are outputted in the classification process.


An adaptive-coherence light source for hyperspectral, topographic, and flow-contrast imaging
Paper 10871-34

Author(s):  Taylor L. Bobrow, Johns Hopkins Univ. (United States), et al.
Conference 10871: Multimodal Biomedical Imaging XIV
Session PSun: Posters-Sunday
Date and Time: 2/3/2019 5:30:00 PM

Non-polypoid colorectal neoplasms often go undetected in routine colonoscopies due to the limited information provided by conventional white light imaging. We present the first benchtop colonoscope with multiple red-green-blue coherent light sources for color, topography, and speckle contrast flow imaging with the goal of increasing lesion detection. Using photometric stereo endoscopy and laser speckle flow contrast algorithms, tissue topography is reconstructed and vasculature contrast is enhanced; both are potential indicators of otherwise subtle lesions. High spatial-frequency, qualitative depth maps of cecum and colon phantoms are reconstructed and speckle flow phantoms are utilized to demonstrate increased contrast of flow regions.


Pre-clinical validation of transrectal diffuse optical tomography in monitoring photocoagulation progression during photothermal therapy
Paper 10871-41

Author(s):  Celina L. Li, Univ. Health Network (Canada), et al.
Conference 10871: Multimodal Biomedical Imaging XIV
Session PSun: Posters-Sunday
Date and Time: 2/3/2019 5:30:00 PM

This study focuses on optimizing and validating a diffuse optical tomography (DOT) instrument incorporating a purpose-designed transrectal probe as a minimally-invasive technique to monitor and control photothermal therapy (PTT) of focal prostate cancer. Studies are presented in preclinical canine prostate models ex vivo and in vivo, with and without porphyrin-lipid nanoparticle enhancement, as well as in other normal tissues, correlating changes in the spatially-resolved DOT signals with the tissue temperature determined by magnetic resonance imaging (MRI)-based thermometry. The use of TR-DOT to localize and delineate tumor by the nanoparticle contrast is also presented.


Assessment of fresh lung tissue using higher harmonic generation microscopy
Paper 10882-85

Author(s):  Laura M. van Huizen, Vrije Univ. Amsterdam (Netherlands), et al.
Conference 10882: Multiphoton Microscopy in the Biomedical Sciences XIX
Session PSun: Posters-Sunday
Date and Time: 2/3/2019 5:30:00 PM

For patients with lung cancer, fast diagnosis and precise excision of lung tumor tissue is important. A great improvement would be an imaging technique that can assess lung tissue with a speed that enables ‘live’ feedback to the surgeon while she/he operates. Higher harmonic generation microscopy (HHGM) meets these requirements. We showed that HHGM generate high quality 3D images with a submicron resolution in less than a minute, without processing the tissue. HHGM revealed the key components of human and mouse lung tissue. This is the first step to validate the HHG microscope for the assessment of fresh unprocessed lung tumor tissue.


Multimodal multiphoton microscopy for visualizing topical drug formulations delivery to human skin
Paper 10882-88

Author(s):  Alexander Fast, Massachusetts General Hospital (United States), et al.
Conference 10882: Multiphoton Microscopy in the Biomedical Sciences XIX
Session PSun: Posters-Sunday
Date and Time: 2/3/2019 5:30:00 PM

Our group has recently developed a method for characterizing distribution of a topical drug within skin using two-photon fluorescence lifetime imaging (FLIM) and phasor analysis. Here, we expand on this work by describing a multimodal approach for rapidly visualizing multiple components in tissue using FLIM and coherent Raman imaging (CRI). By employing a non-Euclidian FLIM phasor analysis for a three-component system informed with the vibrational signature of one of the components retrieved with CRI, we were able to semi-quantitatively describe the spatial distribution of drugs in tissue with molecular specificity and cellular resolution.


Endoscopic multimodal biophotonic imaging foresophageal tracking
Paper 10878-125

Author(s):  Zak Ali, Technische Univ. München (Germany), et al.
Conference 10878: Photons Plus Ultrasound: Imaging and Sensing 2019
Session PSun: Posters-Sunday
Date and Time: 2/3/2019 5:30:00 PM

Presentations of esophageal cancer occur late in the disease, attributing to 400,000 annual deaths worldwide. Today white light endoscopy is a prominent technique in the detection of cancer entailing quadrat random biopsies. This protocol is laborious, plagued with missed cancers and the cost of analyzing biopsies is spiraling. We present a hybrid panoramic photonic endoscope employing multi-spectral optoacoustic tomography (MSOT) and optical coherence tomography (OCT) for esophageal tracking(ESOTRAC). OCT delivers superficial micron-scale morphological imaging and MSOT offers pathophysiological imaging and ability to penetrate deeper than OCT. ESOTRAC will perform in-vivo early diagnosis and staging by replacing 2D qualitative and user dependent observations with objective, quantitative, 3D measurements of the entire esophagus wall, delivering morphological and pathophysiological cancer and pre-cancer features not available to white light endoscopy.


Development of a hemispherical-shaped array sensor for a photoacoustic imaging system
Paper 10878-142

Author(s):  Katsumi Ohira, Japan Probe Co., Ltd. (Japan), et al.
Conference 10878: Photons Plus Ultrasound: Imaging and Sensing 2019
Session PSun: Posters-Sunday
Date and Time: 2/3/2019 5:30:00 PM

In order to obtain a three-dimensional image with high resolution by photoacoustic tomography, a ultrasonic sensor needs to realize the three properties that we should get over as follows; (1) hemispherical-shaped array, (2) multi-channel, (3) broadband of sensitivity. We developed a new fabrication technology that combines the mold method with the flexible sheet of piezoelectric transducers and realized a hemispherical shape sensor that has 1024 channels within a hemispherical shape with a diameter of 110mm. The flexible sheet was made of 1-3 composite transducer and its center frequency is 3.34MHz with 85% bandwidth. This work was funded by ImPACT Program of Council for Science, Technology and Innovation (Cabinet Office, Government of Japan).


Relationship between biochemical haemoglobin levels and optoacoustic tomography parameters at variable biological conditions
Paper 10878-160

Author(s):  Lina Hacker, Univ. of Cambridge (United Kingdom), et al.
Conference 10878: Photons Plus Ultrasound: Imaging and Sensing 2019
Session PSun: Posters-Sunday
Date and Time: 2/3/2019 5:30:00 PM

Optoacoustic tomography (OT) enables the detection of blood haemoglobin (HB) concentration and oxygenation with high contrast and resolution. Here, we studied the impact of biological variations in HB on OT data. Total haemoglobin and oxygen saturation were quantified in vitro using tissue-mimicking agar phantoms and in vivo in mice exposed to different experimental conditions. Biochemical blood parameters were assessed using a haematology analyser. We found OT to be highly sensitive to HB changes in vitro, however, the sensitivity of OT to intra-species HB differences was impaired in vivo. Further work is needed to explore these discrepancies.


Biophotonic approach to tumor in situ vaccination
Paper 10879-1

Author(s):  Mladen Korbelik, BC Cancer Research Ctr. (Canada), et al.
Conference 10879: Biophotonics and Immune Responses XIV
Session 1: PDT and Immune Responses
Date and Time: 2/4/2019 8:00:00 AM

Currently highly regarded approaches for cancer treatment include interventions that not only ablate tumors but also secure in situ vaccination against the targeted lesion. Biophotonic approaches have proven effective in delivering light energy for ablative destruction of tumor masses stimulating immune response in situ. Two main impacts from the light energy absorption in tumor tissue are thermal and oxidative stress. Both provoke in cancer cells a response based on the activity of cell stress signaling networks engaging a variety of protection mechanisms for dealing with the inflicted trauma. Such activities lay the foundation for the in situ tumor vaccination.


Oxygen sensing films to detect inflammation
Paper 10863-1

Author(s):  Conor L. Evans, Wellman Ctr. for Photomedicine (United States), et al.
Conference 10863: Photonic Diagnosis, Monitoring, Prevention, and Treatment of Infections and Inflammatory Diseases 2019
Session 1: Photonic Diagnosis I
Date and Time: 2/4/2019 8:00:00 AM

Infection causes a host of changes within tissue, from cell and tissue death to inflammation. Infection is typically marked by the recruitment of immune cells to the site of injury, which in skin is marked by the typical presentation of turgescence (swelling) and erythema (redness). Problematically, skin infections can present as general, nonspecific symptoms that could arise due to a number of non-related conditions. A simple-to-use diagnostic approach for the detection of skin infection would be high beneficial, saving physician time and effort and aiding the prompt diagnosis of skin infections. Interestingly, we have found that the recruitment and residence of immune cells within the tissue leads to an increase in local tissue oxygen consumption, a physiological change that can be detected by monitoring tissue oxygen tension, or pO2. We make use of a wearable, flexible, and breathable bandage that can be applied to skin for the detection of oxygenation changes induced by mock infections. It is our aim for this approach to be applicable to skin infections, such as cellulitis.


Antibiotic-derived molecular probes for bacterial imaging
Paper 10863-2

Author(s):  Mark A. Blaskovich, The Univ. of Queensland (Australia), et al.
Conference 10863: Photonic Diagnosis, Monitoring, Prevention, and Treatment of Infections and Inflammatory Diseases 2019
Session 1: Photonic Diagnosis I
Date and Time: 2/4/2019 8:30:00 AM

Bacterial infections are becoming an increasing concern due to the rise of drug-resistant bacteria. While much attention is focused on developing better therapies, improving diagnosis would allow for rapid initiation of optimal treatment, reducing unnecessary antibiotic use. One strategy to improve therapeutic treatment outcomes is to rapidly detect the location of potential infections and monitor their treatment. We will present our efforts to develop imaging agents that selectively bind to bacteria, derived from antibiotics initially functionalized with fluorophores for detection. Preliminary experiments to develop probes suitable for whole body imaging of infections (such as PET scans) will also be described.


Intraoperative cross-polarization OCT in glioma surgery: matching with preoperative diffusion tensor MR imaging and fiber tractography
Paper 10868-15

Author(s):  Elena B. Kiseleva, Privolzhsky Research Medical Univ. (Russian Federation), et al.
Conference 10868: Advanced Biomedical and Clinical Diagnostic and Surgical Guidance Systems XVII
Session 5: Surgical Guidance I
Date and Time: 2/4/2019 8:40:00 AM

The cross-polarization (CP) OCT was used in this study for intraoperative differentiation both between tumor and cortex, tumor and white matter, and the structure of white matter itself. Totally, 556 images from 17 patients with different degree of gliomas were obtained from three areas of interest: cortex, white matter and tumor. The CP OCT signal characteristics were compared with preoperative diffusion tensor MR imaging and fiber tractography data. Intraoperative CP OCT helped to clarify the tumor margins with the cerebral cortex, the presence of tumor infiltration areas in the white matter after resection, and confirmed the absence of the tumor tissue in eloquent brain areas, which allowed to justify the tumor removal and avoid a postoperative neurological deficit.


Combined treatment of photosensitizer and gene therapy in nanoparticles for oral cancer treatment
Paper 10879-3

Author(s):  Yih-Chih Hsu, Chung Yuan Christian Univ. (Taiwan), et al.
Conference 10879: Biophotonics and Immune Responses XIV
Session 1: PDT and Immune Responses
Date and Time: 2/4/2019 8:50:00 AM

Human squamous cell carcinoma is the major type of oral cancer. Traditional methods for human oral cancers treatments are surgery, chemotherapy and radiotherapy. Because photodynamic therapy is a noninvasive alternative for oral cancer therapy. A novel photosensitizer was first constructed in nanoparticles, for photodynamic therapy. Oncogene silencing RNA was encapsulated into nanoparticles to silence oncogene expression. Two treatments were combined for cancer treatment.Results suggest that the combination therapy could be a potential treatment to develop for human oral cancer in the future.


Multiphoton imaging and OCT MA for diagnosis of human melanocytic lesions
Paper 10882-15

Author(s):  Elena V. Zagaynova, Privolzhsky Research Medical Univ. (Russian Federation), et al.
Conference 10882: Multiphoton Microscopy in the Biomedical Sciences XIX
Session 5: FLIM/FRET/FCS I
Date and Time: 2/4/2019 8:50:00 AM

In our study we combined three imaging modalities (OCT MA, MPT and FLIM) for in vivo differentiation of benign and malignant melanocytic lesions. Forty patients with 40 pigmented lesions were included. For In vivo examinations a spectral domain OCT system (1.3 μm wavelength, imaging speed of 20,000 A-scans/sec) and multiphoton tomograph MPTflex™ with FLIM module were used. OCT MA shows, that the vessel density and total length of ≥50-μm-diameter vessels increased significantly in the case of melanoma. MPT analysis provided to distinguish benign nevi and melanoma base on morphological features of skin cells. FLIM imaging revealed the specific metabolic changes in cancer cells in comparison with benign cells.


Near infrared photoimmunotherapy for cancer: enhanced anti-tumor immunity when combined with immuno-activation therapies
Paper 10893-1

Author(s):  Hisataka Kobayashi, National Cancer Institute (United States), et al.
Conference 10893: Reporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications XI
Session 1: Imaging and Therapies
Date and Time: 2/4/2019 9:00:00 AM

Near infrared photoimmunotherapy (NIR-PIT) is a new type of molecularly-targeted cancer photo-therapy, which employs a NIR silica-phthalocyanine, IR700, conjugated to a monoclonal antibody targeting cell-surface molecules. NIR-PIT targeting EGFR using the cetuximab-IR700 conjugate is now in transition to fast-track Phase 3 trial in late-stage head and neck squamous cell cancer patients. I will focus on NIR-PIT combined with an immune-checkpoint inhibitor that could treat not only local tumors but also distant untreated tumors without recurrence. This regimen of NIR-PIT could yield vaccination effect against some of treated cancer cells that would be the ultimate form of NIR-PIT in oncology clinic.


RTBioT: A real-time healthcare monitoring Bio-IoT device employing spatially resolved near infrared (NIR) spectroscopy
Paper 10874-3

Author(s):  Sehwan Kim, College of Medicine, Dankook Univ. (Korea, Republic of), et al.
Conference 10874: Optical Tomography and Spectroscopy of Tissue XIII
Session 1: Advances in Methods and Instrumentation I
Date and Time: 2/4/2019 9:00:00 AM

This paper describes RTBioT, one of the first Internet of Things (IoT) healthcare devices based on spatially resolved near infrared spectroscopy to support non-invasively in quantifying chromophores in the biological tissue. Bluetooth Low Energy is used as the primary communication protocol, an IR-enhanced Si PIN photodiode is for a light-receiving element, and a compact fiber-stub type beam combiner is employed as a multiple wavelengths light-emitting source. Most of all, a lock-in amplifier enables accurate measurement of small modulated signals by using phase-sensitive detection technique (PSD). To demonstrate the feasibility for the IoT-based healthcare platform, we conducted an experiment through a tumor-mimicking silicon phantom and human subjects and confirmed that it is enabled to monitor the biological signals and the concentrations of tissue chromophores in real time fashion


Real-time delineation of cancer margins in otolaryngologic applications using multispectral FLIm
Paper 10868-16

Author(s):  Brent W. Weyers, Univ. of California, Davis (United States), et al.
Conference 10868: Advanced Biomedical and Clinical Diagnostic and Surgical Guidance Systems XVII
Session 5: Surgical Guidance I
Date and Time: 2/4/2019 9:00:00 AM

Autofluorescence lifetime imaging is a powerful non-invasive and label-free technique for characterizing biological tissues. The sensitivity of this imaging modality for detecting modest changes in tissue biochemistry and structure hold promise for differentiating among healthy and pathological tissue. Our clinical implementation of multispectral time-resolved autofluorescence measurements have demonstrated promising initial results which enable cancerous and normal tissue to be differentiated on the basis of lifetime and intensity ratios both pre- and post-resection. Our initial data suggests that time-resolved autofluorescence may serve as a valuable tool for providing real-time intraoperative diagnosis and surgical guidance during robot-assisted cancer removal in otolaryngologic applications.


Speckle based sensing of chemicals by an acoustic excitation in aqueous solutions
Paper 10895-19

Author(s):  Zeev Zalevsky, Bar-Ilan Univ. (Israel), et al.
Conference 10895: Frontiers in Biological Detection: From Nanosensors to Systems XI
Session 6: Light, Sound, Heat
Date and Time: 2/4/2019 9:10:00 AM

The optical activity of glucose in aqueous solutions offers a very high specificity in detecting the presence of glucose. In this presentation we will present several concepts for non-invasive detection of glucose, being realized in -vitro as well as in -vivo. In all cases the sensing concept is based upon analysis of time changing spatial statistics of back scattered speckle patterns when being analyzed by properly defocused optics. We will focus on an experimental approach in which we try to employ contactless measurement of acoustic excitations in solutions containing various chemical while using analysis of those time changing speckle pattern. Solutions containing glucose should response differently than those where glucose is absent. To perform this measurement, we excited acoustic waves in a solution and measured the changes in the speckle pattern. The basic concept is that while the solution is acoustically excited the acoustic waves modulate the density of the fluid under examination. This modulation will have two effects on the speckle pattern, the first is a spatial and time-varying modulation of the effective refractive index, and the second is a spatial and time-varying modulation of the optical rotation which is induced by the presence of glucose. Both of these effects should change the speckle pattern, which if recorded with an exposure time which is longer than the acoustic period, will be seen as a smearing of the pattern. By analyzing properties such as speckle size, contrast and/or correlation between images, it is possible to extract a signal which is proportional to the amplitude of the acoustic excitation.


Non-invasive spectral analysis of osteogenic and adipogenic differentiation in adipose-derived stem cells using dark-field hyperspectral imaging technique
Paper 10890-47

Author(s):  Nishir Sanatkumar Mehta, Louisiana State Univ. (United States), et al.
Conference 10890: Label-free Biomedical Imaging and Sensing (LBIS) 2019
Session 9: Polarization and Dark-Field Imaging
Date and Time: 2/4/2019 9:10:00 AM

Mesenchymal stem cells derived from adult adipose tissue possess the regenerative capability to differentiate into adipocytes, osteocytes, and chondrocytes which in turn can be developed into adipose tissues, cartilages, and bones. In the present study, dark-field based hyperspectral Imaging (HSI) technique has been utilized to image single as well as multiple osteoblasts and adipocytes in salt media grown on the glass substrate. The spectral-based study in visible-NIR range would lead to a high-throughput identification of patient-specific derived cells for clinical use preventing mass rejection, and advance our understanding of the behavior of stem cellular clusters undergoing adipogenic and osteogenic differentiation.


Active demodulation schemes for circular ranging optical coherence tomography
Paper 10867-4

Author(s):  Norman Lippok, Wellman Ctr. for Photomedicine (United States), et al.
Conference 10867: Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XXIII
Session 1: Advances in Technology I
Date and Time: 2/4/2019 9:15:00 AM

In Fourier-domain optical coherence tomography, finite acquisition bandwidths can limit the achievable imaging range, axial resolution, and/or imaging speed. Circular ranging (CR) methods were recently demonstrated to overcome these barriers. To avoid overlap of artefacts, CR is performed through the combination of a frequency comb optical source and the use of complex demodulation. In this work, we describe the extension of active demodulation schemes to CR OCT systems using acousto-optic modulators and phase modulators. We highlight the limitations when existing active demodulation schemes are applied naively to CR systems and highlight CR-specific alterations that overcome these limitations.


Development of photoacoustic tomography for intraoperative tumor margin assessment for breast-conserving surgery
Paper 10868-17

Author(s):  Lawrence C. Yip, Western Univ. (Canada), et al.
Conference 10868: Advanced Biomedical and Clinical Diagnostic and Surgical Guidance Systems XVII
Session 5: Surgical Guidance I
Date and Time: 2/4/2019 9:20:00 AM

Current breast-conserving surgery (BCS) re-excision rates average 10-25%. Surgeons can have difficulty accurately locating and excising a tumor. We propose photoacoustic tomography (PAT), an imaging technique with the strengths of ultrasound and optical imaging. With this method, 3D images with high contrast, high resolution and excellent penetration depth can be achieved while remaining low cost. The goal of this project is to develop a portable system to image excised tumors intraoperatively for assisting tumour margin assessment. This imaging approach provides advantages not currently offered by current guidance techniques and has immense potential to lower both patient burden and healthcare costs.


A co-axial projection surgical navigation system for breast cancer sentinel lymph node mapping: system design and clinical trial
Paper 10868-18

Author(s):  Peng Liu, Univ. of Science and Technology of China (China), et al.
Conference 10868: Advanced Biomedical and Clinical Diagnostic and Surgical Guidance Systems XVII
Session 5: Surgical Guidance I
Date and Time: 2/4/2019 9:40:00 AM

Near infrared imaging has been used in the breast tumor resection surgery for sentinel lymph node mapping. However, surgeons need to watch a screen to see the invisible fluorescence. We developed a navigation system that projects the fluorescence back to the surgical site visibly in real-time. A co-axial optics design guarantees the projection accuracy. Phantom and animal experiments are conducted to verify the performance. Furthermore, the system is tested in a clinical trial of ninety patients in three hospitals in China. The navigation process is compared with a commercialized NIR imaging system. The results show a 100% detection rate of sentinel lymph node and good clinical feasibility of the co-axial projection system.


Ultra-fast frequency domain diffuse optical spectroscopy combined with for real-time chromophore extractions for intravital hemodynamic monitoring.
Paper 10874-6

Author(s):  Darren M. Roblyer, Boston Univ. (United States), et al.
Conference 10874: Optical Tomography and Spectroscopy of Tissue XIII
Session 1: Advances in Methods and Instrumentation I
Date and Time: 2/4/2019 9:50:00 AM

We present a new technique called digital DOS (dDOS) that utilizes custom made ultra-fast digital electronics to extract multi-wavelength tissue optical properties over a broad modulation frequency sweep (50-400 MHz) at high speeds (97 Hz) and with high accuracy. We will describe our methods for the extraction of amplitude and phase in firmware, and the implementation of a deep neural network based inversion model that provides real-time streaming of chromophores. In the near term, we anticipate this technique will provide real-time visualization of a broad-array of hemodynamic parameters in the intensive care unit, reducing the need for invasive vascular catheters.


A combined autofluorescence and laser speckle contrast imaging system for parathyroid surgical guidance
Paper 10868-20

Author(s):  Emmanuel A. Mannoh, Vanderbilt Univ. (United States), et al.
Conference 10868: Advanced Biomedical and Clinical Diagnostic and Surgical Guidance Systems XVII
Session 6: Surgical Guidance II
Date and Time: 2/4/2019 10:50:00 AM

Post-surgical hypoparathyroidism is a major complication after thyroid surgery, due to damage to healthy parathyroid glands. Autofluorescence imaging and laser speckle contrast imaging (LSCI) have been separately shown to address the two causes of parathyroid function loss – accidental removal, and damage to the parathyroid blood supply respectively. Here, we present an instrument that combines both techniques to enable intraoperative parathyroid identification and viability assessment. Algorithms were developed to automate the extraction of viability information from speckle contrast images using fluorescence data. The device was tested on ex vivo parathyroid and thyroid specimens, as well as intraoperatively in patients undergoing parathyroidectomy.


Enhanced light microscopy for the direct detection of high-consequence viruses
Paper 10863-9

Author(s):  John H. Connor, Boston Univ. (United States), et al.
Conference 10863: Photonic Diagnosis, Monitoring, Prevention, and Treatment of Infections and Inflammatory Diseases 2019
Session 2: Photonic Diagnosis II
Date and Time: 2/4/2019 11:00:00 AM

The ability to directly identify and characterize infectious diseases directly from patient samples is a constant need, especially for high consequence viruses like Ebola virus, Marburg virus and Lassa virus, which often occur sporadically and in areas where there are few medical resources. To address this need we are developing a reflectance imaging technology (SP-IRIS) that allows the direct detection and characterization of virus particles in serum and plasma using straightforward light microscopy approaches. Our approach allows the detection of high consequence viruses along with their unique virion morphologies within a multiplex detection assay that shows high sensitivity and specificity. Our approach can create rapid “fingerprint” diagnostics for these diseases.


Bioessential chalcogenides and immunological applications: an in vitro exploration of Selenium nanoparticles as potential carriers and therapeutic agents
Paper 10892-27

Author(s):  Brandy Vincent, The Univ. of Texas at San Antonio (United States), et al.
Conference 10892: Colloidal Nanoparticles for Biomedical Applications XIV
Session 9: Applications of Nanoparticles in Cancer Theranostics
Date and Time: 2/4/2019 11:00:00 AM

Selenium (Se) and Tellurium (Te) based chalcogenides are believed to function as potent target mediators. They are believed to operate within diseased biological systems effectively without imposing cytotoxic effects on non-diseased biological systems. Through the reduction of ROS production and preservation of genetic integrity, SexTel-x alloys offers a viable therapeutic cancer agent that is synergistically compliant.


Characterizing the progression of intestinal inflammation and fibrosis with acoustic resolution photoacoustic endoscope: a longitudinal study in vivo
Paper 10878-32

Author(s):  Hao Lei, Univ. of Michigan (United States), et al.
Conference 10878: Photons Plus Ultrasound: Imaging and Sensing 2019
Session 6: Inside the Body: Endoscopy and Intervention
Date and Time: 2/4/2019 11:15:00 AM

Distinguishing inflammatory and fibrotic intestinal strictures in Crohn’s disease (CD) has been a clinical challenge, as the latter has to be surgically resected. In this study, an endoscopic acoustic resolution photoacoustic (PA) microscopy probe was examined with a rabbit model of intestinal strictures in vivo. The experiment results demonstrate that the probe can differentiate the normal (n=7), pure inflammatory (n=5) and mixed inflammatory and fibrotic (n=6) intestinal strictures with statistical significance (p<0.02). Longitudinal observation of intestinal fibrosis has shown a correlation of 0.8 between the increase of PA signal intensity and the time of disease induction in the animals.


Brillouin microscopy for tissue and cell biomechanics
Paper 10890-52

Author(s):  Giuliano Scarcelli, Univ. of Maryland, College Park (United States), et al.
Conference 10890: Label-free Biomedical Imaging and Sensing (LBIS) 2019
Session 11: Spectroscopy and Scattering II
Date and Time: 2/4/2019 11:15:00 AM

Brillouin spectroscopy has been widely used for decades to characterize material mechanical properties. However, due to the weakness of its signal, it was never considered viable in biomedicine. Developing a spectrometer with million-fold improved throughput and combining it with a confocal microscope, we developed Brillouin microscopy, a 3D imaging modality that uses the longitudinal modulus as contrast mechanism for imaging and demonstrated its application in a variety of fields from ophthalmology to cellular biomechanics.


Tomographic Cherenkov-excited luminescence scanned imaging based on back-projection reconstruction demonstrates 0.3mm spatial resolution for molecular reporter through 2-3cm of tissue
Paper 10862-44

Author(s):  Mengyu Jia, Stanford Univ. (United States), et al.
Conference 10862: Molecular-Guided Surgery: Molecules, Devices, and Applications V
Session 10: Optical-Radiation Symposium II
Date and Time: 2/4/2019 11:20:00 AM


Laser immunotherapy for effective melanoma treatment
Paper 10879-9

Author(s):  Shuhong Qi, Huazhong Univ. of Science and Technology (China), et al.
Conference 10879: Biophotonics and Immune Responses XIV
Session 2: Photoimmunotherapy
Date and Time: 2/4/2019 11:30:00 AM

Photothermal therapy combined with immunoadjuvants is advantageous in the personalized cancer immunotherapy. As photothermal treatment in the local tumor offers complete antigen to the immune system which has been stimulated by immunoadjuvants and induce strong antitumor immune response to prevent tumor recurrence and inhibit tumor metastases. Here, we developed a strategy which combined 980 nm laser and an immunoadjuvant to treat the B16 tumor.


On the impact of spectral calibration for biomedical research using spectral filter array cameras
Paper 10885-9

Author(s):  Jacob Renzo Bauer, Norwegian Univ. of Science and Technology (Norway), et al.
Conference 10885: Optical Diagnostics and Sensing XIX: Toward Point-of-Care Diagnostics
Session 2: PPG Imaging Approaches
Date and Time: 2/4/2019 11:30:00 AM

Quantitative spatial oxygenation measurements remain an open challenge. Most commonly used spectral imaging systems rely on temporal sampling of the sensed wavelength. Spectral filter array (SFA) cameras have the potential to measure spectra spatially resolved and in real time. Nevertheless particular aspects and postprocessing steps for SFA cameras have to be taken into account to assure useful biomedical readings. This includes careful suppression of noise, application specific and optimal choice of spectral channels, spatial and spectral corrections and an adequate interpretation of the measured spectra. The influences of processing steps on oxygenation measurements with a commercially available SFA camera in an occlusion of the upper arm experiment are investigated in this research.


Simultaneous photoacoustic imaging and white light video endoscopy for guiding laparoscopic surgery
Paper 10878-33

Author(s):  Rehman Ansari, Univ. College London (United Kingdom), et al.
Conference 10878: Photons Plus Ultrasound: Imaging and Sensing 2019
Session 6: Inside the Body: Endoscopy and Intervention
Date and Time: 2/4/2019 11:30:00 AM

Photoacoustic endoscopy (PAE) has many potential applications in clinical imaging as it can visualize depth-resolved microvasculature with high contrast due to high optical absorption of haemoglobin. We present a clinically-applicable PAE probe capable of high resolution volumetric imaging in a forward-viewing configuration. The probe is implemented using a MEMS scanning mirror and lens relay system with a transparent high-finesse Fabry-Pérot ultrasound sensor at its distal end. The probe has been characterized using a variety of phantoms and ex vivo tissues and shown to provide excellent high resolution 3D vascular images.


Bedside anticoagulation monitoring during cardiac surgery with a drop of whole blood
Paper 10868-23

Author(s):  Diane M. Tshikudi, Massachusetts General Hospital (United States), et al.
Conference 10868: Advanced Biomedical and Clinical Diagnostic and Surgical Guidance Systems XVII
Session 6: Surgical Guidance II
Date and Time: 2/4/2019 11:50:00 AM

Summary Activated clotting time (ACT), used to assess anticoagulation during Cardiac surgery, correlates poorly with heparin concentration and lacks information on key coagulation metrics including fibrin polymerization (α-angle) and clot strength (MA). Here, we assessed the accuracy of our novel bedside optical sensor, iCoagLab, to measure anticoagulation from temporal speckle intensity fluctuations in 25µL of blood during cardiac surgery. Studies, conducted using blood from Cardiac surgery patients showed a dose-dependent prolongation and significant modulation of iCoagLab-ACT throughout surgery which closely mirrored standard-reference TEG, ISTAT-ACT and Hepcon-ACT. In conclusion, iCoagLab accurately measured anticoagulation and global hemostasis using a drop of blood, likely opening the opportunity for multifunctional coagulation monitoring at the bedside during surgery.


Intraoperative surgical applications of snapshot hyperspectral imaging
Paper 10890-55

Author(s):  Itai Katz, Children's National Health System (United States), et al.
Conference 10890: Label-free Biomedical Imaging and Sensing (LBIS) 2019
Session 11: Spectroscopy and Scattering II
Date and Time: 2/4/2019 12:10:00 PM

Snapshot hyperspectral imaging (HSI) is a technique to capture hyperspectral images with a single exposure. While this method has been used extensively in astronomy, applications in other domains have been rare. In this work we describe a custom fabricated snapshot imager and associated medical applications for real-time, intraoperative settings. We construct a camera consisting of a single housing containing a visible and infrared sensor, linked via a beam splitter. In front of each sensor is a Bayer-like array with 16 (visible) and 25 (infrared) filters, arranged in a grid pattern. An HSI sensor is ideal for medical imaging as it is non-invasive and non-ionizing. There is currently an unmet need for examining anatomical structures beyond the visible human spectrum, especially in a manner that is unobtrusive to the surgical workflow. We present three clinical applications: 1) Brain Tumor segmentation, 2) Organ identification and differentiation, 3) Oxygen saturation monitoring in vivo.


Preclinical multimodal imaging of bacterial infections on medical implants
Paper 10863-11

Author(s):  Kevin P. Francis, PerkinElmer, Inc. (United States), et al.
Conference 10863: Photonic Diagnosis, Monitoring, Prevention, and Treatment of Infections and Inflammatory Diseases 2019
Session 3: Photonic Diagnosis III
Date and Time: 2/4/2019 1:30:00 PM

Bacteria such as methicillin-resistant Staphylococcus aureus (MRSA) have increased in prevalence in hospitals over the last three decades. Such bacteria are particularly problematic in postoperative infections, exacerbating treatment through the development of biofilms, especially on medical implants which are virtually impossible to treat without removal and replacement of the device. Non-invasive preclinical optical imaging is being used to better understand the establishment and development of bacterial infections in vivo, and how best to treat them. This technology is also being tested for translated into the clinic.


A multiplexed platform for point of care diagnostics based on optical waveguide technology
Paper 10895-25

Author(s):  Christopher Myatt, MBio Diagnostics, Inc. (United States), et al.
Conference 10895: Frontiers in Biological Detection: From Nanosensors to Systems XI
Session 8: Photonics II
Date and Time: 2/4/2019 1:40:00 PM

Optical waveguides are an optimal platform for on-the-spot biosensors. Optical signal transduction provides high discrimination. The use of evanescent wave illumination, where the light field extends a fraction of the wavelength above a sensor surface, provides a clean signal for surface reactions with minimal background. By illuminating a volume extending above the surface by a few hundred nanometers, evanescent wave sensors often don’t require wash steps or other sample processing complexities. The cost of optical technology has been reduced considerably over the past decade. These factors combine to make for a very practical biosensor design. We will present the architecture and design features of the MBio Diagnostics LightDeck® evanescent planar waveguide sensor, and two of the applications where these practical features enable commercial devices: testing for antibiotic residues in milk, and tests to manage sepsis.


3D cellular imaging of the cornea with Gabor-domain optical coherence microscopy
Paper 10867-14

Author(s):  Cristina Canavesi, LighTopTech Corp. (United States), et al.
Conference 10867: Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XXIII
Session 3: Ophthalmology I
Date and Time: 2/4/2019 1:45:00 PM

A Gabor-domain optical coherence microscope (GDOCM) for 3D imaging with 2-micrometer invariant lateral and axial resolutions and a 15-mm working distance was developed. GDOCM was used to image corneal tissue inside the viewing chamber used for storage. A flattening algorithm was implemented to obtain an en face view of the endothelium. The GDOCM images were compared with those acquired with a specular microscope used in eye banks, and endothelial cell density was evaluated. 3D imaging of the entire thickness of the cornea with cellular resolution over a large field of view (1 mm^2) is a key feature of GDOCM.


Ultrahigh speed ophthalmic SS-OCT angiography at 800 kHz A-scan rate using a VCSEL light source
Paper 10867-15

Author(s):  Oscar M. Carrasco-Zevallos, Massachusetts Institute of Technology (United States), et al.
Conference 10867: Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XXIII
Session 3: Ophthalmology I
Date and Time: 2/4/2019 2:00:00 PM

Optical coherence tomography angiography (OCTA) provides depth-resolved images of vasculature in the retina and choroid without dyes, but OCTA requires repeated scanning of the same transverse position, leading to potentially long acquisition times which may limit clinical utility. We report on ultrahigh speed ophthalmic SS-OCT angiography at 800 kHz A-scan rate using a VCSEL light source. We demonstrate OCTA scan protocols enabled by ultrahigh speed SS-OCT for assessing human retinal and choroidal vasculature structure and function. We present representative data from healthy adult volunteers and patients with ocular diseases to demonstrate clinical viability.


The Twente Photoacoustic Mammoscope 2: instrument optimization and 3D vascular network visualization
Paper 10878-37

Author(s):  Sjoukje M. Schoustra, Univ. Twente (Netherlands), et al.
Conference 10878: Photons Plus Ultrasound: Imaging and Sensing 2019
Session 7: Special Session: Best Paper Award Competition I
Date and Time: 2/4/2019 2:00:00 PM

We present the Twente Photoacoustic Mammoscope 2 (PAM 2) based on a 3D tomographic geometry. A breast is pendant in an imaging tank with water, where 12 curved ultrasound arrays (center frequency 1 MHz) are mounted, each following the breast contour. Illumination occurs from multiple directions with 755 nm and 1064 nm. Breasts of healthy volunteers were imaged to optimize instrument parameters. Three-dimensional images of breast contour, nipple and blood vessel networks within the breast could be observed with high contrast and unprecedented detail. With the knowledge gained from this study we will perform imaging on breast cancer patients.


Cell integrated biosensors: from single cell analysis to organ on a chip
Paper 10891-35

Author(s):  Chenzhong Li, Florida International Univ. (United States), et al.
Conference 10891: Nanoscale Imaging, Sensing, and Actuation for Biomedical Applications XVI
Session 4: Multifunctional Nanoparticles (Imaging and Sensing)
Date and Time: 2/4/2019 2:10:00 PM

This lecture will outline our recent research activities for the fundamental study of physical and electrical properties of cells, as well as the development of a new generation of cell/organ on chips that combine aspects of “top-down” nanofabrication approach with a “bottom-up” self-assembly method for cell and tissue measurements.


High sensitivity SLIM imaging to correlate sperm morphology and fertility outcomes
Paper 10887-46

Author(s):  Mikhail E. Kandel, Univ. of Illinois (United States), et al.
Conference 10887: Quantitative Phase Imaging V
Session 11: QPI of Cells and Tissues III
Date and Time: 2/4/2019 2:10:00 PM

Fluorescence-based cell sorting instruments are capable of classifying sperm for desired characteristics such as gender. It is not surprising that, as these techniques are approaching clinical use, closer scrutiny has revealed that the sorting process introduces a signification increase in oxidative stress in addition to an undesired selection bias due to fragmented DNA. Although some of the damage can be attributed to rough mechanical handling, from studies on adherent cells, it is well known that these defects are also associated with the intrinsic toxicity of the fluorescence labels. In effect, fluorescence-based markers reduce viability, motivating the use of intrinsic contrast methods. Here we present recent progress on evaluating reproductive outcomes using Spatial Light Interference Microscopy (SLIM) for high sensitivity phase imaging. We compared our label-free markers to existing staining techniques. We show how the compatibility of our system with fluorescence/color image acquisition allows our techniques to be used concurrently rather than as an alternative, to conventional methods.


Leukocyte dynamics in cutaneous acute graft-versus-host disease by noninvasive laser confocal video microscopy: a cross-sectional pilot study
Paper 10885-13

Author(s):  Inga Saknite, Vanderbilt Univ. Medical Ctr. (United States), et al.
Conference 10885: Optical Diagnostics and Sensing XIX: Toward Point-of-Care Diagnostics
Session 3: Optical Imaging of Blood
Date and Time: 2/4/2019 2:20:00 PM

In this cross-sectional pilot study, we explore the feasibility of in vivo imaging of leukocyte-endothelial interactions to detect acute graft-versus-host disease (aGVHD) in patients after stem cell transplantation. Our preliminary data of five aGVHD patients and five controls (no aGVHD) 50±30 days post-transplant show that the following quantitative dynamic parameters can be extracted: blood flow velocity, number and velocity of rolling leukocytes, and number of adherent leukocytes.


Wide-field intraoperative Raman imaging technique to guide cytoreductive surgery for advanced stages of ovarian cancer
Paper 10890-59

Author(s):  Sandryne David, Ecole Polytechnique de Montréal (Canada), et al.
Conference 10890: Label-free Biomedical Imaging and Sensing (LBIS) 2019
Session 12: Spontaneous Raman II
Date and Time: 2/4/2019 2:25:00 PM

Ovarian cancer is the fifth most deadly cancer among women in North America. Because this type of cancer is often diagnosed late, the first step is often surgery. Therefore, there is a need for a new imaging technique that can detect cancer tissue with high specificity and sensitivity during cytoreductive procedures. We developed an intraoperative wide-field Raman spectroscopy imaging system to be used alongside tissue classification models trained to recognize cancer tissue using artificial intelligence techniques. These developments pave the way for a new generation of wide-field Raman spectroscopy techniques for macroscopic tissue characterization during surgery.


Non-invasive monitoring of circulating melanoma cells by in vivo photoacoustic flow cytometry
Paper 10879-13

Author(s):  Xunbin Wei, Shanghai Jiao Tong Univ. (China), et al.
Conference 10879: Biophotonics and Immune Responses XIV
Session 3: Monitoring of Immune Activities
Date and Time: 2/4/2019 2:30:00 PM

Melanoma cells have high light absorption due to melanin highly contained in melanoma cells. This property is employed for the detection of circulating melanoma cell by in vivo photoacoustic flow cytometry (PAFC), which is based on photoacoustic effect. PAFC can employ high melanin content of melanoma cells as endogenous biomarkers to detect circulating melanoma cells in vivo. We have developed in vitro experiments to prove the ability of PAFC system of detecting photoacoustic signals from melanoma cells. For in vivo experiments, we have constructed a model of melanoma tumor bearing mice by inoculating highly metastatic murine melanoma cancer cells, B16F10 with subcutaneous injection. PA signals are detected in the blood vessels of mouse ears in vivo. By counting circulating melanoma cells termly, we obtain the number of circulating melanoma cells as melanoma metastasized. Those results show that PAFC is a noninvasive and label-free method to detect melanoma metastases in blood or lymph circulation.


Local outlier factor based iterative outlier removal to reduce image artifacts in ultrasound guided diffuse optical tomography
Paper 10874-13

Author(s):  K. M. Shihab Uddin, Washington Univ. in St Louis (United States), et al.
Conference 10874: Optical Tomography and Spectroscopy of Tissue XIII
Session 3: Diffuse Optical Tomography
Date and Time: 2/4/2019 2:30:00 PM

Measurements errors caused by tissue heterogeneity may introduce artifacts in reconstructed absorption maps in Ultrasound guided Diffuse Optical Tomography. A new two-step algorithm is proposed to iteratively identify and remove measurement outliers based on assignment of local outlier factors and hence to reduce image artifacts and produce more consistent absorption maps among different wavelengths. In first step, measurements were ranked based on data density and the local outlier factor which is the probability of each measurement being an outlier. In second step, outliers are iteratively removed until normalized pattern correlation of different wavelength absorption maps is beyond a specified threshold.


Laser cooling of solids: towards biomedical applications
Paper 10936-21

Author(s):  Quentin Mermillod, Univ. Grenoble Alpes (France), et al.
Conference 10936: Photonic Heat Engines: Science and Applications
Session 5: Characterization Methods and Novel Concepts in Laser Cooling
Date and Time: 2/4/2019 2:30:00 PM

Focal cooling is a promising alternative therapy for intractable focal epilepsies, avoiding the irreversible neuronal damages induced by resection surgery. However, due to thermal conduction losses, local cooling of a deep brain region remains a challenging objective for thermoelectric or fluidic technologies. Here, we investigated the viability of an optical microcooler based on anti-Stokes refrigeration of ytterbium doped YLF crystals, taking into account the medical constraints for implantable device. We realized significant cooling under atmospheric pressure and developed a solution drastically reducing the harmful fluorescence heating of brain-like liquids below 2°C, demonstrating the relevance of this technology for biomedical applications.


Identification of diabetic patients via urine analysis by FTIR: preliminary study
Paper 10863-14

Author(s):  Luís Felipe Chagas e Silva Carvalho, Univ. de Taubate (Brazil), et al.
Conference 10863: Photonic Diagnosis, Monitoring, Prevention, and Treatment of Infections and Inflammatory Diseases 2019
Session 3: Photonic Diagnosis III
Date and Time: 2/4/2019 2:45:00 PM

Diabetes is a chronic disease that affects millions of people every year worldwide. In this paper, a semi-portable Bruker Alpha ATR-FTIR was employed to analyse zing urine samples of 7 patients (3 normal, 2 diabetics and 2 pre-diabetics) in order to distinguish these three groups based on their urine spectrochemical information. Cross-validated principal component analysis, coupled with linear discriminant analysis was applied to the spectra set, resulting in 94% total accuracy, showing the potential of ATR-FTIR as a potential new tool for identification of diabetics in clinical environments, whereby diagnosis can be performed in a rapid, non-invasive and automated way.


Using vascular optical tomography imaging (VOTIS) to monitor peripheral arterial disease in patients who received a surgical intervention
Paper 10874-14

Author(s):  Alessandro Marone, Columbia Univ. (United States), et al.
Conference 10874: Optical Tomography and Spectroscopy of Tissue XIII
Session 3: Diffuse Optical Tomography
Date and Time: 2/4/2019 2:50:00 PM

Peripheral artery disease is caused by an accumulation of plaque in arteries, which leads to stenosis. In advanced cases, surgery is performed to re-establish blood flow to the extremities. Therefore, accurate monitoring the blood flow in the feet of these patients is crucial. VOTIS was used to assess perfusion in 4 different angiosomes of 29 patients who underwent a surgical intervention. Dynamic optical imaging was performed just before the intervention, 4 hours later and 1 month later. We found a strong correlation between the dynamic shapes of the total hemoglobin signals and long-term outcome of the procedure.


Estimating retinal vascular permeability from human fluorescein videoangiography data: Optimization and sensitivity analysis of kinetic models
Paper 10863-15

Author(s):  Elif Kayaalp Nalbant, Illinois Institute of Technology (United States), et al.
Conference 10863: Photonic Diagnosis, Monitoring, Prevention, and Treatment of Infections and Inflammatory Diseases 2019
Session 3: Photonic Diagnosis III
Date and Time: 2/4/2019 3:00:00 PM

A quantitative tracer kinetic modeling approach is demonstrated to be capable of estimating vascular permeability from retinal fluorescein videoangiography data (collected routinely in clinical ophthalmology). The sensitivity analysis and early results in a human study, provide encouraging results for widespread adoption of this approach as an early indicator of progression to retinopathy in patients with diabetes.


A new method based on frequency-domain optical tomography to diagnose joints affected by systemic lupus erythematosus
Paper 10874-15

Author(s):  Alessandro Marone, Columbia Univ. (United States), et al.
Conference 10874: Optical Tomography and Spectroscopy of Tissue XIII
Session 3: Diffuse Optical Tomography
Date and Time: 2/4/2019 3:10:00 PM

It is estimated that in the USA 1.5 million people suffer from systemic lupus erythematosus (SLE). 90% of these are women. This autoimmune disease often involves joints, and more than 90% of those affected will experience joint pain, stiffness and swelling. We explored the clinical utility of frequency-domain optical tomography to distinguish finger joints affected by SLE from healthy ones of volunteers. First results of the analysis of the amplitude and phase shift of the images acquired show a sensitivity of 80% and a specificity of 92% to distinguish between joints of healthy volunteers and SLE patients.


Studying the roundworm Caenorhabditis elegans using microfluidic chips
Paper 10875-43

Author(s):  Martin Gijs, Ecole Polytechnique Fédérale de Lausanne (Switzerland), et al.
Conference 10875: Microfluidics, BioMEMS, and Medical Microsystems XVII
Session 10: Applications
Date and Time: 2/4/2019 3:40:00 PM

Caenorhabditis elegans nematodes are traditionally cultured on agar plates seeded with E. coli bacteria as food. Microfluidics promises precise spatio-temporal handling of biological reagents for more controlled manipulation and culture of worms and embryos. I will first discuss reversible worm immobilization protocols for high-resolution on-chip imaging. We have also realized worm bio-communication assays on-chip, microfluidic chips for automated embryo arraying, phenotyping, and long-term live imaging, as well as for drug studies performed during early embryogenesis. Microfluidic chips have allowed to study worm populations at individual animal resolution and to investigate individualized multi-phenotypic responses to drugs and genetic cues.


Multispectral endoscopy for early detection of dysplasia in Barrett’s oesophagus (MuSE): a pilot study
Paper 10868-25

Author(s):  Dale J. Waterhouse, Univ. of Cambridge (United Kingdom), et al.
Conference 10868: Advanced Biomedical and Clinical Diagnostic and Surgical Guidance Systems XVII
Session 8: Cancer Applications
Date and Time: 2/4/2019 3:50:00 PM

Multispectral imaging (MSI) allows simultaneous collection of morphological (spatial) and biochemical (spectral) information from tissue, which can help to more effectively delineate disease. A compact, clinically translatable multispectral endoscope (MuSE) was designed to collect multispectral images during endoscopic surveillance of patients with Barrett’s oesophagus. Subjects due to undergo clinically indicated endoscopy with a previous diagnosis of dysplasia or early adenocarcinoma were enrolled for experimental imaging in a pilot clinical study. Here, we present the results from these first-in-human tests of MuSE, including evaluation of the image quality and classification potential of the multispectral image cubes.


Diffuse optical non-destructive organ risk (DONOR) indexing of significant liver pathology: does the surface measurement represent the parenchyma measurement?
Paper 10874-16

Author(s):  Daqing Piao, Oklahoma State Univ. (United States), et al.
Conference 10874: Optical Tomography and Spectroscopy of Tissue XIII
Session 4: Applications to Liver, Kidney, Breast, Intestine
Date and Time: 2/4/2019 4:00:00 PM

We demonstrate a diffuse optical non-destructive organ risk (DONOR) indexing method for identifying significant liver pathology from 27 human livers not accepted to transplantation (OUHSC IRB #8155). A portable lab-on-a-crate diffuse optical spectroscopy device with a 3mm source-detector separation was used for measurements on 5 sites on liver surface and cross-section. For the cross-sectional parenchyma of the right lobe alone, DONOR index≥1.5 identified all six livers with fibrosis stage ≥2 and one liver with necrosis=5. Surface measurements differ from parenchyma measurements at various levels due to capsule. DONOR indexing of liver pathology is promising, but requiring unsheilding the capsular effect.


Optoelectronic measurement of respiration rate and its relationship with oxygen take-up
Paper 10885-18

Author(s):  Sijung Hu, Loughborough Univ. (United Kingdom), et al.
Conference 10885: Optical Diagnostics and Sensing XIX: Toward Point-of-Care Diagnostics
Session 4: Optical Absorption Techniques for Human and Veterinary Applications
Date and Time: 2/4/2019 4:10:00 PM

The work has established a dynamic relationship between respiration rate (RR) and oxygen up-take (V'O2) which has led to the development of an approach that uses a single device to assess continuously the physiological state of athletes in order to help prevent overtraining and so reduce the risk of injury. The RR was extracted from raw photoplethysmographic signals by means of a bespoke opto-electronic patch sensor (mOEPS) and the variations of V'O2 were captured by a cardiopulmonary exercise testing device (Vyntus™ CPX Metabolic, CareFusion, Germany).


A fast and reproducible ELISA laser platform for highly-sensitive IL-6 analysis
Paper 10895-30

Author(s):  Xiaotian Tan, Univ. of Michigan (United States), et al.
Conference 10895: Frontiers in Biological Detection: From Nanosensors to Systems XI
Session 9: Advanced Sensing Methods II
Date and Time: 2/4/2019 4:20:00 PM

We developed a novel on-chip ELISA laser platform by directly fabricating micro-wells on dielectric mirrors for immunosorbent reactions. Polystyrene microbeads of 30 μm in diameter were placed in the wells to optically stabilize the resonance cavity during laser measurements. With this design, highly sensitive IL-6 quantification (LOD ~100 fg/ml for IL-6) was achieved with short assay time (~1.5 hours, 30 minutes for laser measurements), small sample volume (~20 μL), and high repeatability.


Utilizing deep learning technology to develop a novel CT image marker for categorizing cervical cancer patients at early stage
Paper 10879-17

Author(s):  Yuchen Qiu, The Univ. of Oklahoma (United States), et al.
Conference 10879: Biophotonics and Immune Responses XIV
Session 4: Novel Detection Technology
Date and Time: 2/4/2019 4:25:00 PM

We developed an innovative CT image marker to accurately stratify cervical cancer patients. The marker is accomplished by a novel hybrid scheme consisting of a pre-trained deep neural network (i.e. AlexNet) for tumor feature extraction, a dimension reduction algorithm (i.e. discriminate neighborhood embedding) for feature optimization, and a machine learning based classifier (i.e. support vector machine) for marker generation. Using receiver operator characteristic (ROC) curve as assessing index, the result shows that this marker yielded an area under the ROC curve (AUC) of 0.75±0.01, which indicates the potential of this new marker for the precision treatment of cervical cancer patients.


Towards improved longitudinal evaluation of inflammation and infection in free-breathing animals of lung disease through advancing intravital microscopy in a multimodal imaging approach
Paper 10863-18

Author(s):  Greetje Vande Velde, KU Leuven (Belgium), et al.
Conference 10863: Photonic Diagnosis, Monitoring, Prevention, and Treatment of Infections and Inflammatory Diseases 2019
Session 4: Photonic Diagnosis IV
Date and Time: 2/4/2019 4:30:00 PM

To investigate inflammation, infection and novel treatment options, investigators typically rely on end-stage procedures on isolated tissues from animal models that only provide a snapshot of processes that are essentially dynamic in time and space. Therefore, imaging technology allowing to repeatedly evaluate host response (inflammation, tissue remodeling) and infection is indispensable to evaluate the dynamics of disease progression and treatment. We developed groundbreaking integrated imaging approaches involving intravital fibered confocal fluorescence microscopy, whole-body optical and multimodal imaging to acquire novel observations and insights in inflammatory versus pathogen-related disease progression and therapy effects in live animal models of fungal lung infection.


Effect of thermoregulation during physical activity on physiological state using multi-wavelength opto-electronic measurement
Paper 10885-19

Author(s):  Sijung Hu, Loughborough Univ. (United Kingdom), et al.
Conference 10885: Optical Diagnostics and Sensing XIX: Toward Point-of-Care Diagnostics
Session 4: Optical Absorption Techniques for Human and Veterinary Applications
Date and Time: 2/4/2019 4:30:00 PM

Thermoregulation should be taken into consideration as a crucial factor in evaluating the status and functionalities of the cardiovascular system. This study aims to investigate how thermoregulation impacts on cutaneous microcirculation and analyse the correlation between the opto-physiological signal components and skin temperature during physical activity, by means of a multi-wavelength opto-electronic patch sensor (mOEPS). A combination of four wavelength illuminations were used to produce multiplexed physiological parameters and explore correlations of physiological variations through the implementation of an exercise protocol. Preliminary results have expressed that physiological status is affected by human thermoregulation with different physical activity intensities.


Polarization sensitive optical coherence tomography guided intra-cardiac radiofrequency ablation in living swine
Paper 10867-23

Author(s):  Xiaowei Zhao, Case Western Reserve Univ. (United States), et al.
Conference 10867: Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XXIII
Session 4: Intravascular, Pulmonary and GI
Date and Time: 2/4/2019 4:30:00 PM

Cardiac arrhythmias have become a major health issue in western countries. Catheter-based radiofrequency ablation (RFA) enables the curative treatment of cardiac arrhythmias. However, the RFA procedure is only guided with indirect information, which may result in poor quality lesions and lead to arrhythmia recurrence or complications. Our previous work has demonstrated that an integrated polarization-sensitive optical coherence tomography-RFA catheter can guide catheter-tissue apposition and monitor lesion formation in vitro. In this study, we verified the integrated catheter’s functionality in living swine. The results show that in addition to procedural guidance, the integrated catheter may also help avoid complications.


Real-time surface-tracking handheld probe for intraoperative brain cancer mapping using quantitative OCT
Paper 10868-27

Author(s):  Hyeon-Cheol Park, Johns Hopkins Univ. (United States), et al.
Conference 10868: Advanced Biomedical and Clinical Diagnostic and Surgical Guidance Systems XVII
Session 8: Cancer Applications
Date and Time: 2/4/2019 4:30:00 PM

Quantitative OCT has been demonstrated for human brain cancer detection based on an attenuation mapping method. However, the attenuation coefficient analysis relies on depth-dependent OCT intensity profile and is thus sensitive to tissue surface position relative to imaging beam focus, and a steady tissue surface is challenging to maintain during surgery. We report a surface-tracking handheld probe in order to reliably maintain a steady beam focus position inside the target tissue during surgery. A compact linear motor was integrated with a handheld OCT imaging probe and a real-time feedback control was generated from tissue surface detection from OCT A-scan signals.


High spatial frequency imaging texture analysis differentiates tumor from normal breast tissue subtypes
Paper 10874-18

Author(s):  Samuel S. Streeter, Thayer School of Engineering at Dartmouth (United States), et al.
Conference 10874: Optical Tomography and Spectroscopy of Tissue XIII
Session 4: Applications to Liver, Kidney, Breast, Intestine
Date and Time: 2/4/2019 4:40:00 PM

A recent clinical study involved the prospective collection of multispectral, high spatial frequency structured light imaging data of 70 freshly excised breast tumor specimens containing a total of 69 benign and 51 malignant tissue regions of interest. Regions of interest were delineated and diagnosed by a pathologist via histological analysis and were co-registered to the image data in a conservative fashion. Power spectral density curve slope and intercept parameterization and texture parameters of contrast, correlation, energy, and homogeneity calculated from a gray-scale co-occurrence matrix provide statistically significant (p<0.05) differentiation between benign and malignant tissue types.


Biophotonics in veterinary medicine: the first steps
Paper 10885-20

Author(s):  Blaž Cugmas, Univ. of Latvia (Latvia), et al.
Conference 10885: Optical Diagnostics and Sensing XIX: Toward Point-of-Care Diagnostics
Session 4: Optical Absorption Techniques for Human and Veterinary Applications
Date and Time: 2/4/2019 4:50:00 PM

Clinically useful biophotonic techniques can directly benefit human health and well-being. Also, animal welfare has recently become important what is especially evident with pets like dogs and cats. Despite this fact, the occurrence of biophotonics in veterinary medicine is low. In this study, we presented key biophotonic studies in veterinary medicine, which applied spectroscopy, photoplethysmography (PPG), and photodynamic therapy. Additionally, with a cooperation with scientific and clinical veterinarians, we investigated various veterinary challenges, which could be potentially addressed by the biophotonic techniques. Opportunities were found in canine and feline dermatology, oncology, and cardiology, and in equine orthopedics. We believe that this study will promote biophotonics to a new scientific area.


Characterization of vascular dynamics using hybrid photoacoustic-ultrasound imaging through in-vitro modeling and in-vivo small animal imaging
Paper 10875-46

Author(s):  Subhamoy Mandal, Deutsches Krebsforschungszentrum (Germany), et al.
Conference 10875: Microfluidics, BioMEMS, and Medical Microsystems XVII
Session 10: Applications
Date and Time: 2/4/2019 4:50:00 PM

Photoacoustic imaging has enabled researchers to study vascular profiles and dynamics in small animal tumor models in vivo. However, there is a need for cross-validation of the results and development of simulation platforms to accurately study the flow-dynamics in vitro. We have used low cost shrinky dinks (pre-stretched Polystyrene sheets) to fabricate microfluidic chips that mimic blood vessels, and used them to study flow profiles and blood- contrast agent mixing. Results were corroborated with in vivo small animal (kidney) perfusion imaging using hybrid photoacoustic/ultrasound imaging.


In vivo assessment and diagnosis of fibrotic lung disease with optical coherence tomography
Paper 10867-25

Author(s):  Lida P. Hariri, Massachusetts General Hospital (United States), et al.
Conference 10867: Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XXIII
Session 4: Intravascular, Pulmonary and GI
Date and Time: 2/4/2019 5:00:00 PM

Idiopathic pulmonary fibrosis (IPF) is a fatal form of fibrotic interstitial lung disease (ILD). Diagnosis of IPF is essential to determine prognosis and the most effective therapy for patients, but often requires invasive surgery. We aim to determine whether endobronchial OCT can serve as a low-risk method for in vivo IPF diagnosis. We performed OCT imaging in vivo in ILD patients undergoing biopsy for diagnosis. OCT was able to visualize diagnostic IPF features, including dense destructive fibrosis and cystic honeycombing, and distinguish these from non-IPF features. These findings support the potential of OCT as a minimally-invasive method for IPF diagnosis.


A 3D printed centrifugal microfluidic platform for solid-phase-extraction and fluorescent detection of spilled oil in water
Paper 10875-47

Author(s):  Wanjun Wang, Louisiana State Univ. (United States), et al.
Conference 10875: Microfluidics, BioMEMS, and Medical Microsystems XVII
Session 10: Applications
Date and Time: 2/4/2019 5:10:00 PM

A novel centrifugal microfluidic platform for solid-phase-extraction (SPE) and fluorescence detection of oil in water is designed, fabricated, and tested. Mechanical pinch valves were used to manipulate flows of the sample and reagents. The valving system was simply controlled by the rotation frequency of the centrifugal platform. The prototype of the proposed system was 3D printed with PLA as the material. The test was conducted with 10ppm standard oil-water sample. Different stationary sorbent were used and compared. The experiment results showed that the fluorescence intensity of the sample was significantly increased. This platform can be potentially used as a portable on-situ enrichment and detection device for various of pollutant in environment water.


Optical molecular imaging as a quantitative tool for malaria vaccine development
Paper 10863-20

Author(s):  Clarize M. de Korne, Leiden Univ. Medical Ctr. (Netherlands), et al.
Conference 10863: Photonic Diagnosis, Monitoring, Prevention, and Treatment of Infections and Inflammatory Diseases 2019
Session 4: Photonic Diagnosis IV
Date and Time: 2/4/2019 5:15:00 PM

Live-attenuated malaria parasites (sporozoites; spz) are most promising as vaccine candidates against malaria. Their efficacy, however, depends on the migration ability of the spz. Little is known about the spz migration patterns within human skin. In this study, fluorescence microscopy was used to quantify migration patterns in vitro and in human skin explants. Image analysis revealed that spz motility depends on its environment, displaying more complex directional movement in skin versus in vitro. However, radiation-attenuated vaccine spz displayed less directional movement as compared to wild-type spz. These migrational deficits could explain the reduced vaccine efficacy observed in human trials.


Intranasal µOCT quantifies the functional microanatomical airway defect in cystic fibrosis patients
Paper 10867-26

Author(s):  Hui Min Leung, Wellman Ctr. for Photomedicine, Massachusetts General Hospital (United States), et al.
Conference 10867: Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XXIII
Session 4: Intravascular, Pulmonary and GI
Date and Time: 2/4/2019 5:15:00 PM

Cystic fibrosis (CF) is characterized by severely impaired mucociliary clearance, and the study of the associated defects in mucociliary transport apparatus calls for a high-resolution imaging technique capable of capturing the dynamic mucociliary activity along the airways. We recently used an intranasal 1-µm-resolution OCT imaging technology (µOCT) to study the functional microanatomy of the upper airways of both CF and healthy human subjects in vivo. Here, we present the latest advancements in this technology, data analysis, and results showing striking differences in many aspects of the functional microanatomical measurements obtained in CF and control subjects.


Evaluation of electron densities of a soft tissue equivalent multi-material loaded phantom using a phase retrieval method
Paper 10879-20

Author(s):  Muhammad U. Ghani, The Univ. of Oklahoma (United States), et al.
Conference 10879: Biophotonics and Immune Responses XIV
Session 4: Novel Detection Technology
Date and Time: 2/4/2019 5:30:00 PM

One of the important goal of x-ray phase sensitive imaging is to provide quantitative information such as tissue’s phase maps and electron densities while improving tissues contrast. Various phase retrieval methods have been developed for this task and one such method is based on the phase attenuation duality (PAD) principle. With an inline based phase sensitive imaging prototype, the phase maps and electron tissue densities of a multi-material loaded phantom were evaluated using the PAD-based method and compared to the theoretical estimates. The phantom consists of several disk inserts each with 1 cm diameter mimicking different parts like lung, adipose, breast and solid water. Phase sensitive images of the phantom were acquired at 120 kV, 3.35 mAs with a 50 µm focal spot size under a geometric magnification (M) of 2.2. With necessary data processing with the PAD generated images, phase maps and electron density of each material of the phantom were determined. The accurate quantitative information may provide the physicians an additional tool in the correct identification of a cancer disease.


Electrical muscle stimulation to improve tissue contact for catheter-based endoscopic imaging and therapy
Paper 10867-27

Author(s):  Tan H. Nguyen, Massachusetts Institute of Technology (United States), et al.
Conference 10867: Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XXIII
Session 4: Intravascular, Pulmonary and GI
Date and Time: 2/4/2019 5:30:00 PM

Uniform circumferential contact between catheters and the mucosa is challenging in optical coherence tomography (OCT) imaging and therapeutic applications. We investigated the feasibility of electrical muscle stimulation (EMS) to improve tissue coverage in catheter-based endoscopic applications in swine. We demonstrate a balloon-based OCT imaging catheter integrated with a flexible circuit for EMS that simultaneously performed ultrahigh speed OCT to assess esophageal contractility. Different stimulation parameters and electrode spacings were tested to minimize EMS current while achieving sufficient stimulation. Multiple datasets were acquired for each set of parameters to assess repeatability. Future work will evaluate safety for clinical use.


Flexible optical imaging bands for the assessment of systemic lupus erythematosus in finger joints
Paper 10885-37

Author(s):  Youngwan Kim, Columbia Univ. (United States), et al.
Conference 10885: Optical Diagnostics and Sensing XIX: Toward Point-of-Care Diagnostics
Session PMon: Posters-Monday
Date and Time: 2/4/2019 5:30:00 PM

We have developed a system of flexible optical imaging bands that can be used to assess the effects of systemic lupus erythematosus (SLE) on finger joints. Two of these bands were wrapped around PIP joints of 11 SLE patients and 4 healthy volunteers. 4-minute time traces reflecting the hemodynamic changes generated by inflating and deflating a blood pressure cuff were recorded. Shorter rise times and longer plateau times in the traces were observed in joints of SLE patients, compared to joints of healthy volunteers. Performing a discriminant analysis we obtained a specificity of 89% with a sensitivity of 76%.


Two-photon microscopy of Paneth cells in small intestine, in-vivo
Paper 10879-38

Author(s):  Won Hyuk Jang, Pohang Univ. of Science and Technology (Korea, Republic of), et al.
Conference 10879: Biophotonics and Immune Responses XIV
Session PMon: Posters-Monday
Date and Time: 2/4/2019 5:30:00 PM

Paneth cells are one of the principal epithelial cell types in the small intestine, located at the base of intestinal crypts. Paneth cells play key roles in intestinal host-microbe homeostasis via granule secretion, and their dysfunction is implicated in pathogenesis of several diseases including Crohn’s disease. Despite their physiological importance, study of Paneth cells has been hampered by the limited accessibility and lack of labeling methods. In this study, we developed a simple in vivo imaging method of Paneth cells in the intact mouse small intestine by using moxifloxacin and two-photon microscopy (TPM). Moxifloxacin, an FDA-approved antibiotic, was used for labeling cells and its fluorescence was strongly observed in Paneth cell granules by TPM. Moxifloxacin labeling of Paneth cell granules was confirmed by molecular counterstaining. Comparison of Paneth cells in wild type, genetically obese (ob/ob), and germ-free (GF) mice showed different granule distribution. Furthermore, Paneth cell degranulation was observed in vivo. Our study suggests that TPM with moxifloxacin labeling can serve as a useful tool for studying Paneth cell biology and related diseases.


Electroacoustic tomography for monitoring anti-tumor immune response
Paper 10879-44

Author(s):  Liangzhong Xiang, The Univ. of Oklahoma (United States), et al.
Conference 10879: Biophotonics and Immune Responses XIV
Session PMon: Posters-Monday
Date and Time: 2/4/2019 5:30:00 PM

The non-thermal electric ablation by nanosecond pulsed electric field has been recognized as a potential methodology for the activation of anti-tumor immune response. A novel imaging system, Electroacoustic Tomography (EAT) has been developed to monitor the procedure of electroporation, in vivo, by capturing the acoustic waves induced by the absorption of electric field energy in biological tissues. The system relies on the pulsed, high-potential electrical fields naturally occurring in electroporation process as its energy source for acoustic detection. The energy absorbed by biological tissues will cause local thermal expansion, which propagates through the medium as acoustic waves. Such waves can be detected by ultrasonic transducers with specific frequency, outside of the tissue. By utilizing an array of ultrasonic transducers, real-time imaging can be achieved without the presence of any invasive labeling agents. The system in development has the potential to be a practical imaging modality for monitoring and optimizing the electroporation process for the enhancement of the immune response to cure the cancer.


Augmenting endoscopic instruments with 3D surface imaging
Paper 10868-45

Author(s):  Steven Yi, Xyken, LLC (United States), et al.
Conference 10868: Advanced Biomedical and Clinical Diagnostic and Surgical Guidance Systems XVII
Session PMon: Posters-Monday
Date and Time: 2/4/2019 5:30:00 PM

Traditional endoscope is the most commonly used and inexpensive clinic tool for gastrointestinal (GI) disease diagnosis and treatment. Frequent uses of endoscopes include localization and diagnosis of diseases (e.g. polyps, bleeding, and celiac), biopsy, and assessment of the effectiveness of therapeutic interventions such as radiotherapy of cancer. Unfortunately, today’s endoscopes are single camera based, therefore they provide only two-dimensional visualization. No quantitative measurement capability can be provided. In this presentation, we present an optical fiber bundle enabled 3D surface imaging design based on existing endoscopy platforms. Our design will utilize existing channels in the endoscope. No other modification is needed.


Capsule endoscopy with 720-degree imaging and VR
Paper 10868-46

Author(s):  Steven Yi, Xyken, LLC (United States), et al.
Conference 10868: Advanced Biomedical and Clinical Diagnostic and Surgical Guidance Systems XVII
Session PMon: Posters-Monday
Date and Time: 2/4/2019 5:30:00 PM

Capsule endoscopy (CE) uses a miniature on-board camera in a pill for imaging gastrointestinal (GI) tract. It has provided a non-invasive and non-ionization way for gastroenterologists to diagnose GI tract diseases. However, CE has major drawbacks such as ineffective forward-looking field of view (FOV), abundant data, and lengthy viewing and interpreting time, significantly lowering the chance of finding a GI disease through the video screening process. We present a full spherical field of view imaging and immersive display visualization system for the next generation CE technology. Our design is shown to have significant advantages over existing CE.


Optical diffraction tomography based imaging platform for brain cancer pathology
Paper 10887-60

Author(s):  Renjie Zhou, The Chinese Univ. of Hong Kong (Hong Kong, China), et al.
Conference 10887: Quantitative Phase Imaging V
Session PMon: Posters-Monday
Date and Time: 2/4/2019 5:30:00 PM

Glioma is a deadly brain tumor, and its progression is accompanied with morphological changes of cellular structures. Frozen section is the standard pathological examination method to allow the neurosurgeon to determine the extent of excision during the glioma removal surgery. Due to many complicated steps, frozen section method requires ~ 30 minutes to get the examination result for a well-trained pathologist. To provide an easier and quicker way for determining tumor margin, we propose using ODT for intraoperative pathology of brain tumor. Our preliminary experimental results revealed significant changes in RI distributions from Grade II to Grade IV diffuse glioma.


Improvements in diffuse optical spectroscopic imaging (DOSI) for the measurement of sarcoma tumors
Paper 10874-64

Author(s):  Hannah M. Peterson, Boston Univ. (United States), et al.
Conference 10874: Optical Tomography and Spectroscopy of Tissue XIII
Session PMon: Posters-Monday
Date and Time: 2/4/2019 5:30:00 PM

Diffuse optical spectroscopic imaging (DOSI) is a near-infrared modality that noninvasively measures functional information in thick tissue. Bone and soft tissue cancers (sarcomas), are rare tumors in which volumetric changes may not occur during treatment. DOSI is sensitive to tumor metabolism and necrosis and could provide a new way to stratify treatment groups and monitor chemotherapy response in sarcoma patients. This study describes improvements to the probe design and imaging depth implemented to optimize measurements in sarcoma patients. Probe improvements were guided by multilayer Monte Carlo simulations based on clinical MRI and DOSI data.


Using NIR spectral tomography to predict residual cancer burden of breast cancer during neoadjuvant chemotherapy
Paper 10874-73

Author(s):  Xu Cao, Dartmouth-Hitchcock Medical Ctr. (United States), et al.
Conference 10874: Optical Tomography and Spectroscopy of Tissue XIII
Session PMon: Posters-Monday
Date and Time: 2/4/2019 5:30:00 PM

27 patients were enrolled in a study to investigate whether properties obtained by near infrared spectral tomography (NIRST) can be used to predict residual cancer burden (RCB) after neoadjuvant chemotherapy (NAC) in breast cancer patients. The Pearson correlation coefficients between the percentage change in total hemoglobin (%HbT) and RCB class during the first treatment cycle (0.7, p-value=0.0006), show a strong correlation between RCB and %HbT.


Evaluation of metastatic potential of circulating tumorous calls using quantitative phase imaging (QPI)
Paper 10887-75

Author(s):  Irina Vasilenko, A.N. Kosygin Russian State Univ. (Russian Federation), et al.
Conference 10887: Quantitative Phase Imaging V
Session PMon: Posters-Monday
Date and Time: 2/4/2019 5:30:00 PM

The purpose of this work to evaluate the possibility of quantitative phase imaging for characterization of circulating tumorous cells (CTC). The analysis was carried out of the morphodensitometric biomarkers of the metastatic activity of circulating tumorous cells including spectral parameters of the dynamics of conformational alterations of their nuclear structures. A new information was received about heterogeneity of the circulating tumorous cells with different metastatic activity which allows the broadening of fundamental scientific knowledge concerning cancerogenesis


Multi-wavelength imaging reconstruction using the genetic algorithm in diffuse optical tomography
Paper 10874-77

Author(s):  Chen Xu, New York City College of Technology (United States), et al.
Conference 10874: Optical Tomography and Spectroscopy of Tissue XIII
Session PMon: Posters-Monday
Date and Time: 2/4/2019 5:30:00 PM

A novel image reconstruction method for diffuse optical tomography is proposed in this paper. This method implements the multi-wavelength constraint and genetic global optimization to estimate the average values of lesion area. The estimation is then used as the initial values for conjugate gradient (CG) optimization to reconstruct the oxy-hemoglobin and de-oxyhemoglobin, then total hemoglobin. This method can reduce the effects of noise in the data and remove the artifacts in the reconstruction. Phantom experiments results have shown the total hemoglobin concentrations are constructed with less than 10% error, and clinical date also show good improvement and stability.


A miniature frequency domain diffuse optical optode for quantitative wearable oximetry
Paper 10874-82

Author(s):  Raeef Istfan, Boston Univ. (United States), et al.
Conference 10874: Optical Tomography and Spectroscopy of Tissue XIII
Session PMon: Posters-Monday
Date and Time: 2/4/2019 5:30:00 PM

Current wearable optical technologies generally utilize superficial tissue continuous-wave measurements for biological metrics such as heart rate monitoring. Here we investigate the use of a new multi-wavelength optical laser and compact avalanche photodiode for use in a miniaturized diffuse optical frequency-domain optode. These components represent a highly compact fiberless optode for frequency-domain measurements. The system had high SNR, achieved high accuracy and precision, and was capable of tracking hemodynamics during a cuff occlusion test. This work demonstrates that frequency domain diffuse optical measurements can be achieved in a highly portable format, providing new opportunities for monitoring with quantitative oximetry.


Label-free quantitative mapping of water and lipid content in tissue with shortwave-infrared spatial frequency domain imaging
Paper 10874-84

Author(s):  Yanyu Zhao, Boston Univ. (United States), et al.
Conference 10874: Optical Tomography and Spectroscopy of Tissue XIII
Session PMon: Posters-Monday
Date and Time: 2/4/2019 5:30:00 PM

We will demonstrate that label-free and accurate in vivo quantification of water and lipids is achievable in the shortwave infrared (SWIR) due in part to the overt and distinctive spectral characteristics of these species in the 900-1300 nm wavelength band. We will present data from a new imaging system that utilizes spatial frequency domain imaging (SFDI) in the SWIR wavelength band to generate wide-field maps of lipid and water concentration. We will show that this device is capable of continuous monitoring of edema and inflammation, as well as lipid content through intact skin of both mice and humans.


Low frequency oscillations in foot angiosome using diffuse speckle contrast analysis
Paper 10874-89

Author(s):  Chaebeom Yeo, Daegu Gyeongbuk Institute of Science & Technology (Korea, Republic of), et al.
Conference 10874: Optical Tomography and Spectroscopy of Tissue XIII
Session PMon: Posters-Monday
Date and Time: 2/4/2019 5:30:00 PM

A foot angiosome concept has been proposed for vascular surgery. Low frequency oscillations (LFOs) which related with Mayer wave and vasomotion have been important in hemodynamic and neuronal connectivity studies. In this study, a multi-channel diffuse speckle contrast analysis system investigates the correlations between LFOs from different positions on foot angiosome by cross-correlation analysis. It also attempts to determine physiological sources of LFOs on each angiosome by independent component analysis (ICA). Different delays from the lead-lag relationships of the cross-correlations involving the channel closest to the heart were obtained.


Hyperspectral imaging fluorescence excitation scanning spectral characteristics of control and remodeled mouse arteries
Paper 10890-94

Author(s):  Joshua Deal, Univ. of South Alabama (United States), et al.
Conference 10890: Label-free Biomedical Imaging and Sensing (LBIS) 2019
Session PMon: Posters-Monday
Date and Time: 2/4/2019 5:30:00 PM

Atherosclerosis is responsible for nearly a third of all American deaths annually. Current detection methods are inefficient or nonspecific. Recent advances in hyperspectral imaging could detect changes in the autofluorescence of arteries associated with vessel remodeling and subsequent plaque formation and could detect and classify existing lesions. Here, we present data comparing spectral image characteristics of a mouse model designed to undergo vessel remodeling. Excitation scans utilized wavelengths between 350 nm and 550 nm. Hyperspectral data were generated and analyzed with custom Matlab scripts and visualized in ENVI. Preliminary data suggest consistent spectral features associated with control and remodeled vessels.


Natural history of Barrett’s esophagus using tethered capsule OCT endomicroscopy and portable OCT imaging system: initial experience
Paper 10867-28

Author(s):  Jing Dong, Wellman Ctr. for Photomedicine (United States), et al.
Conference 10867: Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XXIII
Session 4: Intravascular, Pulmonary and GI
Date and Time: 2/4/2019 5:45:00 PM

Tethered capsule endomicroscopy (TCE) is a recently developed technique where a small tethered pill (11 mm x 25 mm) that implements optical coherence tomography (OCT) imaging is swallowed and procures high resolution microscopic images of the esophageal wall. TCE can be performed rapidly ( < 10 mins) in subjects without the need for sedation, greatly simplifying esophageal examination and making it an ideal tool for longitudinal studies due to decreased procedural complexity, time, and cost. To date, pilot, single-center studies have been conducted and demonstrated the feasibility and safety of this technology. In this abstract, we report our early experience with TCE and a portable OCT imaging system in a multi-center, longitudinal clinical study to investigate the microscopic natural history of Barrett’s Esophagus (BE).


Chip-based Raman spectroscopy for microbial sensing
Paper 10873-1

Author(s):  Jürgen Popp, Leibniz-Institut für Photonische Technologien e.V. (Germany), et al.
Conference 10873: Optical Biopsy XVII: Toward Real-Time Spectroscopic Imaging and Diagnosis
Session 1: Optical Bioassay Platforms I
Date and Time: 2/5/2019 8:10:00 AM

Infectious diseases threaten the health of people. The rapid identification of infectious pathogens together with the characterization of their interaction with drugs is crucial for the patient’s survival. Classical microbiological analysis methods rely on time-consuming cultures. Raman spectroscopy together with chip-based sampling strategies offers the potential to bypass time-consuming cultivation and allows for a rapid characterization of microbial pathogens on a single cell level. It will be shown that Raman spectroscopy holds great promise as point-of-care-approach for a rapid monitoring of bacteria in body liquids or for water-, air- and soil monitoring and for the detection of pathogens in food.


Computer vision-based spatial co-registration of spectroscopic measurements for tumour margin delineation
Paper 10868-31

Author(s):  Conor C. Horgan, Imperial College London (United Kingdom), et al.
Conference 10868: Advanced Biomedical and Clinical Diagnostic and Surgical Guidance Systems XVII
Session 9: Technology Development I
Date and Time: 2/5/2019 8:40:00 AM

Accurate tumour margin detection is a crucial step in tumour resection surgeries for progression-free survival. While spectroscopic techniques for margin delineation have shown promise as highly accurate diagnostic systems, they are inherently limited by their point-based application. Here we demonstrate a computer vision-based technique that captures spatial information, enabling the transformation of spectroscopic systems from one-dimensional tools to clinically-relevant two-dimensional diagnostic platforms. We show that through visual tracking of a Raman spectroscopic probe’s location relative to the tissue, we can display spatially co-registered Raman spectroscopic diagnoses over clinical tumour imaging data to enhance tumour margin visualisation and aid tumour resection.


Optimization of light transmission through an excitation-scan hyperspectral mirror array system
Paper 10881-23

Author(s):  Marina Parker, Univ. of South Alabama (United States), et al.
Conference 10881: Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues XVII
Session 5: Biomedical Imaging using a DMD or Other Mirror Array I: Joint Session with 10881 and 10932
Date and Time: 2/5/2019 8:50:00 AM

A 5- Dimensional Rapid Hyperspectral Imaging system is undergoing testing that can provide high-speed live cell imaging. The current design utilizes LEDs, a multifaceted mirror array, and lenses to focus light sources into a liquid light guide. Ideal locations of each component were analyzed with the goal to optimize optical transmission. A model of the system was constructed and tested using Monte Carlo optical ray tracing in TracePro software. LED light sources and lenses were simulated by importing their properties using software tools. Initial results show a transmission increase of 20% is possible.


Drug-resistant catheter-associated urinary tract Infection (CAUTI): an enlightened therapeutic approach
Paper 10863-24

Author(s):  Jeffery A. Gelfand, Massachusetts General Hospital (United States), et al.
Conference 10863: Photonic Diagnosis, Monitoring, Prevention, and Treatment of Infections and Inflammatory Diseases 2019
Session 5: Antimicrobial Photodynamic Therapy
Date and Time: 2/5/2019 8:55:00 AM

Catheter–associated urinary tract infections (CAUTIs) cause millions of infections and thousands of deaths, and is a major reservoir for drug-resistance. We are investigating antimicrobial photodynamic therapy (aPDT), antimicrobial blue light(aBL) and combinations with antibiotics. We catheterized female rats and infected them with uropathogenic E.Coli, infused the bladder with methylene blue (MB) and potassium Iodide (KI), and illuminated the bladder once with a diffusing fiber connected to a 1W 660nm laser. Multilog killing was observed. However, rebound of infection occurred. We are now experimenting with combinations of illumination with antibiotics. With tetracyclines illuminated by bluelight, we saw significant drops in the antibiotic MIC by the combination of light and drug. Multiple treatments with aPDT and aBL, with or without minimal intravesical antimicrobials may solve the problem.


Optical waveguides for on-chip fluorescence measurements
Paper 10885-22

Author(s):  Pao T. Lin, Texas A&M Univ. (United States), et al.
Conference 10885: Optical Diagnostics and Sensing XIX: Toward Point-of-Care Diagnostics
Session 5: On-chip and Paper Optical Biomarker Detection
Date and Time: 2/5/2019 9:00:00 AM

Optical waveguides using a visible transparent nitride were developed to perform fluorescence measurement on a chip. Through finite difference time domain (FDTD) design, the exciting green light was guided by the micron-scale ridge waveguide, while its evanescent wave was expanded outside the waveguide surface and capable to efficiently excite the fluorescent molecules that were approaching the waveguide facets. Since the waveguide was centimeters long, it has a longer fluorescence excitation path comparing to traditional samples prepared for microscopy measurements. As result, the waveguide device was excite the stronger fluorescent signals. In addition, the nitride waveguide was prepared by the complementary metal–oxide–semiconductor (CMOS) process thus enabling high volume manufacturing and reducing the cost of the device fabrication.


Breast tumor appearances in photoacoustic tomography from fine 3D optical-acoustic simulations
Paper 10878-52

Author(s):  Maura Dantuma, Univ. Twente (Netherlands), et al.
Conference 10878: Photons Plus Ultrasound: Imaging and Sensing 2019
Session 9: Image Enhancement: Algorithm, Processing, Modeling, and Machine Learning
Date and Time: 2/5/2019 9:00:00 AM

Multiple in-vivo studies have observed breast tumors in photoacoustic images. The appearance of the tumor does however differ significantly. Both system characteristics as the tumors’ anatomical differences can be the reason. We gain insights into the tumor appearance by performing fine 3D photoacoustic simulations on 3D MRI-segmented breast phantoms with tumors embedded. Both the tumor’s physiology as the systems transducer characteristics are varied to investigate their effects on the tumor appearance.


Slide-free digital pathology with in vivo and ex vivo 3D microscopy platforms
Paper 10883-63

Author(s):  Jonathan T. C. Liu, Univ. of Washington (United States), et al.
Conference 10883: Three-Dimensional and Multidimensional Microscopy: Image Acquisition and Processing XXVI
Session 1: Structured Illumination in Multidimensional Microscopy
Date and Time: 2/5/2019 9:30:00 AM

The gold standard for the detection and diagnosis of diseases is based on the microscopic evaluation of thin tissue sections mounted on glass slides, a time-consuming and labor-intensive process that suffers from sampling errors and artifacts. In order to improve the precision and accuracy of clinical pathology, we are developing both miniature handheld optical-sectioning devices to guide biopsy and surgical treatments, as well as open-top light-sheet microscopes for nondestructive 3D molecular pathology of excised specimens. These technologies have the potential to significantly improve our ability to detect, diagnose, and grade diseases so that patients receive timely and optimized treatments.


A luminescent oxygen-sensing hydrogel for open wounds
Paper 10893-23

Author(s):  Haley L. Marks, Massachusetts General Hospital (United States), et al.
Conference 10893: Reporters, Markers, Dyes, Nanoparticles, and Molecular Probes for Biomedical Applications XI
Session 6: Fluorescent Probes for Imaging
Date and Time: 2/5/2019 9:40:00 AM

Wound healing is currently visually assessed by physicians and commonly requires multiple clinical visits for dressing changes. These are often painful, compromise tissue health, and increases infection risks. Towards treatment guidance, our ‘SMART’ bandage can measure localized oxygen partial pressure in tissue via a clinically validated phosphorescent oxygen-sensing metalloporphyrin incorporated into a hydrogel matrix. The emission of the oxygen-sensing hydrogel can be visualized by the naked eye and its signal was found to increase by an order of magnitude in an oxygen deprived environment (0 mmHg pO2) compared to room air (160 mmHg pO2).


Low-cost diagnostic for monitoring neonatal jaundice in low-resource settings
Paper 10885-24

Author(s):  Pelham Keahey, Massachusetts General Hospital (United States), et al.
Conference 10885: Optical Diagnostics and Sensing XIX: Toward Point-of-Care Diagnostics
Session 5: On-chip and Paper Optical Biomarker Detection
Date and Time: 2/5/2019 9:40:00 AM

Neonatal Jaundice is a common condition in newborns caused by excess bilirubin accumulating in the blood. If left untreated jaundice can cause permanent neurological impairment or death. Jaundice resulting from hyperbilirubinemia can be easily treated using blue light phototherapy, and several treatment systems have been built for low-resource settings. However, there is still a lack of an appropriate low-cost diagnostic. To address this, we present BiliSpec, a low-cost paper disposable and reader to rapidly measure total bilirubin from whole blood. Bilirubin concentrations measured with BiliSpec correlated well with a laboratory reference standard in a 94 patient study (r = 0.973).


Multimodal priors reduce acoustic and optical inaccuracies in photoacoustic imaging
Paper 10878-56

Author(s):  Subhamoy Mandal, Deutsches Krebsforschungszentrum (Germany), et al.
Conference 10878: Photons Plus Ultrasound: Imaging and Sensing 2019
Session 9: Image Enhancement: Algorithm, Processing, Modeling, and Machine Learning
Date and Time: 2/5/2019 10:00:00 AM

Photoacoutic imaging of biological tissues is characterized by depth dependent optical fluence loss and acoustic variations. Here, we aim to correct for these inaccuracies aided by extrinsic imaging priors obtained through concurrent high-frequency ultrasound (US) imaging of tissue samples. We segmented the skin line and characterized tissue components using deformable model-based segmentation from the ultrasound images. The prior information from co-registered US images and tissue temperature was used to accurately model light fluence and speed of sound respectively. Methods applied here show significant improvement in beamforming performance, enhanced visual image quality and a higher PSNR.


Cholesterol esterification inhibition suppresses prostate cancer metastasis by impairing the Wnt/β-catenin pathway
Paper 10873-6

Author(s):  Hyeon Jeong Lee, Boston Univ. (United States), et al.
Conference 10873: Optical Biopsy XVII: Toward Real-Time Spectroscopic Imaging and Diagnosis
Session 2: Optical Bioassay Platforms II
Date and Time: 2/5/2019 10:30:00 AM

Increased lipid accumulation has been observed in multiple types of aggressive cancer cells, but the composition of these lipid droplets remained unclear. This study observed an aberrant accumulation of cholesteryl ester in metastatic lesions using Raman spectroscopic analysis of lipid droplets in human prostate cancer patient tissues. Depletion of cholesteryl ester storage significantly suppresses the development and growth of metastatic cancer lesions in prostate cancer orthotopic and intra-cardiac injection mouse models with negligible toxicity. Gene expression profiling reveals that cholesteryl ester depletion suppresses the metastatic potential through upregulation of multiple regulators that negatively impact metastasis. Additionally, Wnt/β-catenin, a vital pathway for metastasis, is downregulated upon cholesteryl ester depletion. Mechanistically, inhibition of cholesterol esterification significantly blocks secretion of Wnt3a through reduction of monounsaturated fatty acid levels, which limits Wnt3a acylation. These findings open opportunities for diagnosing and treating metastatic prostate cancer by targeting the altered cholesterol metabolism. These preclinical results pave the foundation for further clinical studies.


Spectrally resolved multiphoton microscopy for the identification of biomarkers
Paper 10882-38

Author(s):  Björn-Ole Meyer, DTU Fotonik (Denmark), et al.
Conference 10882: Multiphoton Microscopy in the Biomedical Sciences XIX
Session 12: Second/Third Harmonic Generation Microscopy II
Date and Time: 2/5/2019 10:35:00 AM

We have developed a system capable of resolving Two-Photon Fluorescence Emission (TPFE) and Second Harmonic Generation (SHG) signals with high spectral resolution for the characterization of biomarkers. In Multiphoton Microscopy, the extraction of morphological and functional biological features is typically achieved by separation of signals into different channels using optical filters. In doing so, signal spectra can be unknown or overlapping. Previously the choice of such filters relied on prior knowledge or heuristic testing. Our system allows for the study of biomarkers and therefore enables the appropriate selection of channels, tailored to the application, when building fast diagnostic systems.


Photo-inactivation of Neisseria gonorrhoeae: a paradigm changing approach for combating antibiotic-resistant gonococcal infections
Paper 10863-28

Author(s):  Tianhong Dai, Massachusetts General Hospital, Harvard Medical School (United States), et al.
Conference 10863: Photonic Diagnosis, Monitoring, Prevention, and Treatment of Infections and Inflammatory Diseases 2019
Session 6: Antimicrobial/Anti-Inflammatory Blue Light
Date and Time: 2/5/2019 10:45:00 AM

Neisseria gonorrhoeae is the causative pathogen of gonococcal infection, which is becoming untreatable due to the raising emergence of antibiotic resistance. There is a critical need for the development of new anti-gonococcal approaches. In this study, we investigated, for the first time, the utility of antimicrobial blue light (aBL), an innovative non-antibiotic approach, for the treatment of gonococcal infections. Our findings indicated that aBL at 405-nm preferentially inactivated N. gonorrhoeae over human vaginal epithelial cells. Furthermore, no genotoxicity of aBL to the vaginal epithelial cells was observed at the therapeutic aBL exposure. aBL also effectively inactivated N. gonorrhoeae invaded into the vaginal epithelial cells. The development of resistance to aBL by N. gonorrhoeae did not occur after 20 successive cycles sub-therapeutic inactivation. Endogenous aBL-absorptive photosensitizers (porphyrins and flavins) in N. gonorrhoeae were identified and quantified, with coproporphyrin being the most abundant type of endogenous porphyrin presenting in N. gonorrhoeae. Taken together, 405-nm aBL exhibits great potential in combating antibiotic-resistant gonococcal infection, given the significant drawbacks in current management of this disease.


Depolarization signatures of multiply scattered light
Paper 10867-37

Author(s):  Pelham Keahey, Massachusetts General Hospital (United States), et al.
Conference 10867: Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XXIII
Session 6: Advances in Technology II
Date and Time: 2/5/2019 11:00:00 AM

Lipid-rich atherosclerotic plaques are characterized by a strong depolarization signature when imaged with intravascular polarization sensitive OCT. Here, we investigate the association of multiple scattering with depolarization to verify if it can explain the observed depolarization. With the extended Huygens Fresnel principle we estimate the ratio between the contribution of singly and multiply scattered light to the OCT signal and compare it to the observed depolarization signal in phantom samples. Understanding the mechanism of depolarization seen in liquid-rich plaques may offer insight into the size and concentration of the lipid particles, which would be diagnostically relevant.


Development of pulsed blue light technologies for bacterial biofilm disruption
Paper 10863-29

Author(s):  Violet Bumah, San Diego State Univ. (United States), et al.
Conference 10863: Photonic Diagnosis, Monitoring, Prevention, and Treatment of Infections and Inflammatory Diseases 2019
Session 6: Antimicrobial/Anti-Inflammatory Blue Light
Date and Time: 2/5/2019 11:10:00 AM

The ubiquitous rise of drug-resistant bacteria has heightened the urgent need for novel, non-pharmaceutical antimicrobial agents with the potential to inhibit bacterial growth and biofilm development. Preliminary testing of planktonic cultures using pulsed 450 nm blue light using a printed LED substrate has demonstrated effective bacterial kill. Our team is pursuing bacterial biofilm disruption using pulsed 450nm blue light based on the strain of bacteria, replication cycle and dosages obtained from our prior work. The use of LIVE/DEAD fluorescence has demonstrated the effectiveness of our pulsed 450 nm blue light protocol in suppressing bacterial growth and disrupting biofilm formation.


A 3D semi-anthropomorphic photoacoustic breast phantom
Paper 10878-59

Author(s):  Maura Dantuma, Univ. Twente (Netherlands), et al.
Conference 10878: Photons Plus Ultrasound: Imaging and Sensing 2019
Session 10: International Photoacoustic Standardisation Consortium
Date and Time: 2/5/2019 11:15:00 AM

Photoacoustic (PA) breast imaging systems progressively move into the clinics for in-vivo studies. Next to tumor detection, studies also focus on extracting information about the tumor by performing multi-wavelength PA for quantitative oxygen saturation estimations. Until now, it has been difficult to compare the results from different systems due to the wide variability in system characteristics. In order to do inter-system comparisons and to validate oxygen saturation estimations, a standardized but realistic measurement object is required. We present the first 3D semi-anthropomorphic photoacoustic breast phantom and demonstrate its features both in ultrasound imaging as in 3D PA tomography.


A portable, multi spectral, hand-held spatial frequency domain imaging system for imaging and monitoring of human colorectal cancer
Paper 10874-29

Author(s):  Yifeng Zheng, Washington Univ. in St. Louis (United States), et al.
Conference 10874: Optical Tomography and Spectroscopy of Tissue XIII
Session 6: Spatial Frequency Domain Imaging II
Date and Time: 2/5/2019 11:20:00 AM

A multi-spectral, portable, hand-held LED based spatial frequency domain imaging system was used for ex vivo imaging pretreatment and post treatment human colon and rectal tissues. Freshly excised human colon and rectal tissue samples were imaged with the hand-held SFDI probe with 9 wavelengths extending from visible to NIR (660-950 nm). Important tumor biomarkers such as hemoglobin, scatter amplitude, scatter spectral slope, water and lipid content were quantitatively extracted from the SFDI absorption and scattering images. Significant differences were observed between the absorption as well as scattering distribution of normal, tumor and polyp tissue as well as between pre-treated and post-treated tumors.


Photo-disassembly of membrane microdomains revives a broad spectrum of antibiotics against MRSA persisters
Paper 10863-30

Author(s):  Jie Hui, Boston Univ. (United States), et al.
Conference 10863: Photonic Diagnosis, Monitoring, Prevention, and Treatment of Infections and Inflammatory Diseases 2019
Session 6: Antimicrobial/Anti-Inflammatory Blue Light
Date and Time: 2/5/2019 11:25:00 AM

The prevalence of antibiotic resistance and the presence of bacterial persisters increasingly challenge the successful treatment of Staphylococcus aureus infections, and thus poses a great threat to the global health. Here, we present a photonic approach to revive a broad spectrum of antibiotics for eradication of MRSA persisters via photo-disassembly of staphyloxanthin-enriched functional membrane microdomains. Using high-intensity 460 nm pulsed laser, we achieved strikingly high staphyloxanthin bleaching efficiency and depth, which leads to catastrophic disassembly of membrane microdomains, yielding highly compromised cell membrane with nanometer-scale pores created and PBP2a unanchored from cell membrane or dispersed. This photonic disassembly approach paves a novel platform to revive beta-lactam antibiotics and antibiotics inhibiting intracellular activities.


SERS-active photonic crystal fiber probe: towards next generation biopsy needle
Paper 10885-28

Author(s):  Dinish U.S., Singapore Bioimaging Consortium (Singapore), et al.
Conference 10885: Optical Diagnostics and Sensing XIX: Toward Point-of-Care Diagnostics
Session 6: Raman Spectroscopy and Surface Enhanced Raman for Biomedical Applications
Date and Time: 2/5/2019 11:30:00 AM

A compact and cheap biosensor should always possess high sensitivity to detect biomarkers of diseases at a very low concentration and in some cases even at low sample volume. Here, we demonstrate a highly sensitive biosensing platform using surface enhanced Raman scattering (SERS) coupled with novel nanostructured plasmonic materials incorporated into specially designed photonic crystal fibre (PCF) probes. SERS realises enhanced vibrational Raman ‘fingerprint’ spectra of analyte, which allows simultaneous multiplex detection with very high sensitivity. SERS-PCF probe exploits the advantages of molecular specific Raman spectra, giant signal enhancement by SERS and the flexibility of optical fibres. PCFs with axially aligned air holes helps in the incorporation of liquid analytes into it enables better light confinement, which results in improved interaction volume for the light and the immobilized analyte compared to the conventional planar measurement. This provides an unprecedented sensitivity and measurement reproducibility. We present the initial results from our SERS-PCF probe with optimized design and functionalised with nanostructures for the detection of ovarian cancer biomarker in clinical cyst fluid. We envision that it could be translated as a highly sensitive opto-fluidic fiber biopsy needle that enables one-step integrated sample collection and sensing for diverse end use biomedical applications.


Opto-acoustic colorization of blood oxygenation in biologically relevant phantoms
Paper 10878-60

Author(s):  Jason Zalev, Seno Medical Instruments, Inc. (United States), et al.
Conference 10878: Photons Plus Ultrasound: Imaging and Sensing 2019
Session 10: International Photoacoustic Standardisation Consortium
Date and Time: 2/5/2019 11:30:00 AM

Opto-acoustic imaging is used to visualize blood in biological tissue. This has application in the diagnosis and detection of cancer and other diseases. By using two different optical wavelengths, the blood's oxygenation level can be imaged based on its natural optical contrast, even without injection of any external contrast agent. We analyze the ability of a dual-wavelength opto-acoustic system to display colorized blood oxygenation levels in biologically accurate opto-acoustic phantoms with blood-filled channels. The correlation between colorized results is investigated as oxygen saturation varies. Colorization is demonstrated at depths 1cm, 2cm and 3cm for hematocrit levels 4%, 27% and 41%.


Stimulation of mitochondrial biogenesis and management of all three phases of wound healing, including inflammation through the induction of fluorescence niomodulation using weak fluorescent light energy
Paper 10863-31

Author(s):  Giovanni Scapagnini, Klox Technologies, Inc. (Canada), et al.
Conference 10863: Photonic Diagnosis, Monitoring, Prevention, and Treatment of Infections and Inflammatory Diseases 2019
Session 6: Antimicrobial/Anti-Inflammatory Blue Light
Date and Time: 2/5/2019 11:50:00 AM

In recent years, biomedical research on photobiomodulation (PBM) has led to the development of various light-generating devices, which can benefit a wide range of clinical indications. A novel approach to inducing PBM is through a fluorescence biomodulation-based system, which consists of a broadband blue LED and topical product containing specialized chromophores, which upon illumination, produce weak fluorescent light energy (FLE). In clinical trials, FLE has been shown to modulate both healthy and disease-affected skin, providing a unique method for treating inflammatory skin conditions such as acne and rosacea, and accelerating both chronic and acute wound healing. To better understand the influence that chromophore-induced FLE has on cellular metabolism and inflammatory responses, we studied this system in vivo in murine and canine models and in vitro on Dermal Human Fibroblasts (DHFs). The system was evaluated in a dermal fibrotic mouse model with full-thickness excisional wounds having undergone a split-thickness human skin graft. Accelerated re-epithelialization, reduced neovascularization, myofibroblast and mast cell accumulation, and normalized collagen remodeling were significantly modulated by the system in comparison to the blue LED and untreated control. In dogs suffering from chronic deep pyoderma (canine acne), FLE + standard of care (SOC) treatment significantly reduced time to clinical resolution by half from week 2 onwards (p<0.001) compared to SOC alone. At week 4, animal biopsies showed enhanced mitochondrial biogenesis in the FLE+SOC group vs SOC group, as supported by a statistically significant increase in the number (89.31%) (p<0.0001) and size (90.15%) (p<0.0001) of mitochondria. Modulation of inflammatory pathways, reepithelialisation, and angiogenesis have also been demonstrated. In vitro data from IL-1α/β-stimulated DHFs treated with FLE showed a significant decrease in IL-6 production by 130.14% after 24 hours (p<0.001), compared to a blue LED control group, and returned to baseline after 72 hours. These results support the use of this FLE technology for a variety of skin conditions impacted by inflammation and can offer a promising therapeutic solution to support other medical conditions.


Ultrasonic needle tracking with a high-finesse Fabry-Perot fiber optic hydrophone
Paper 10868-39

Author(s):  Sunish J. Mathews, Univ. College London (United Kingdom), et al.
Conference 10868: Advanced Biomedical and Clinical Diagnostic and Surgical Guidance Systems XVII
Session 10: Technology Development II
Date and Time: 2/5/2019 11:50:00 AM

Ultrasonic needle tracking is a technique for localising the tip of a medical needle relative to an ultrasound imaging probe using an integrated ultrasonic transmitter or receiver. This study had two foci: to increase the sensitivity of an integrated fiber optic hydrophone receiver, and to develop a custom needle stylet that was compatible with clinical practice and adaptable to different needle lengths. We tested the sensitivity of the sensorized stylet across a wide range of needle angulations, depths and insertion angles. We conclude that ultrasonic tracking with high-finesse Fabry-Pérot fiber optic hydrophone is very promising for use in clinical practice.


Current-controlled Nitinol wire for improved arterial navigation
Paper 10868-40

Author(s):  Linda J. Olafsen, Baylor Univ. (United States), et al.
Conference 10868: Advanced Biomedical and Clinical Diagnostic and Surgical Guidance Systems XVII
Session 10: Technology Development II
Date and Time: 2/5/2019 12:10:00 PM

The shape memory alloy Nitinol has a long record of biocompatibility, particularly when used as a coil for stents. Nitinol wire with a programmed heat activation above body temperature is used for improved navigation of arteries for treatment of aneurysms and other medical conditions. We present results of current-controlled steering of Nitinol wire, including programming, control, and material response to varying current levels and pulse durations. We also demonstrate the viability of a light emitting diode attached to the guidewire with additional potential for image guidance, catheter navigation, and other treatment and delivery techniques.


Monocyte subset distribution as risk predictor for coronary heart disease (CHD)
Paper 10881-26

Author(s):  Attila Tárnok, Fraunhofer-Institut für Zelltherapie und Immunologie (Germany), et al.
Conference 10881: Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues XVII
Session 7: Cytomics I
Date and Time: 2/5/2019 1:30:00 PM

There are many established risk predictors for CHD. Atherosclerotic plaques are initiated by peripheral blood monocytes (PBM) maturing at the endothelial wall to macrophages. We quantified PBM subsets to test their value as risk predictors in CHD. 749 healthy German adults (mean age 57 years) from the LIFE study were included. 10-color immunophenotyping was performed and risk assessment done by statistical tests. In summary, it can be supposed that, monocyte count and presence of carotid plaques could be more accurate for CAD risk stratification and more useful for predicting cardiovascular diseases.


Development of miniature hand-held probe for wide-field pediatric ophthalmic OCT angiography imaging
Paper 10867-42

Author(s):  Shaozhen Song, Univ. of Washington (United States), et al.
Conference 10867: Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XXIII
Session 7: Ophthalmology II
Date and Time: 2/5/2019 1:45:00 PM

OCT has proved as a valuable ophthalmic imaging modality, but not often practiced on young children and infants due to its requirements for subject to cooperate and sit still during scans. We report a novel design and operation of a highly integrated miniature handheld OCT probe, with high-speed angiography function that can be used in clinical settings for young children and infants, providing rapid, non-invasive retinal imaging and quantifications of perfusion states. Compared to conventional OCT system, the high-speed hand-held OCT system significantly improved the operator’s experience and scanning efficiency, important for imaging infants.


External AC electric fields optimize the fluorescence enhancement produced by the light-metal-fluorophore interactions
Paper 10881-28

Author(s):  Logeeshan Velmanickam, North Dakota State Univ. (United States), et al.
Conference 10881: Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues XVII
Session 7: Cytomics I
Date and Time: 2/5/2019 2:00:00 PM

Fluorescence is widely used in medical diagnosis as the method of detection and quantifying biomarkers. However, traditional fluorescence enhancement using light-metal-fluorophore interactions produce the detection limits in nano-molar, which is not sufficient to address the needs of medical diagnosis. To address this issue, in this work, we have developed finite element calculation and investigated the use of low frequency external electric fields to maximize the light-metal-fluorophore interactions. Our results show that introduction of electric field could increase the detection limit to attomolar. Therefore, this research will have translational impact on medical diagnosis.


High-speed, ultrahigh-resolution spectral-domain OCT with active reference arm length matching for wide-field retinal imaging
Paper 10867-43

Author(s):  Siyu Chen, Massachusetts Institute of Technology (United States), et al.
Conference 10867: Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XXIII
Session 7: Ophthalmology II
Date and Time: 2/5/2019 2:00:00 PM

We developed an ultrahigh-resolution SD-OCT prototype that were capable of imaging at 250 kHz A-line rate using 148-nm spectral bandwidth and full 2048-pixel sensor resolution. Axial resolution was 2.4 µm in tissue, with 1.6 mm depth range (1.2 mm at -6 dB signal roll-off). We actively modulated the reference arm length to match the curvature of the retina, thus extending the effective axial imaging range, as well as increasing overall signal-to-noise ratio by keeping the image within the optimal Fourier range. High-density line-scan and large field-of-view images revealed fine retinal layered features, demonstrating the system’s high resolution and rapid volumetric imaging capability.


Synergistic inactivation of multidrug-resistant Acinetobacter baumannii by essential oil and blue light
Paper 10863-34

Author(s):  Mei X. Wu, Harvard Medical School (United States), et al.
Conference 10863: Photonic Diagnosis, Monitoring, Prevention, and Treatment of Infections and Inflammatory Diseases 2019
Session 7: Combination Therapy of Light and Other Antimicrobials
Date and Time: 2/5/2019 2:05:00 PM

Development of non-antibiotic modalities is urgently needed to tackle antibiotic resistant microbes. Here, we combined two non-antibiotic approaches to synergistically kill microbes irrespective of their antibiotic sensitivity in both in vitro and in vivo and prior and after biofilm formation. Mechanistically, we found that reactive oxygen species (ROS) were generated at levels in proportion with the synergistic activity in the presence of carvacrol with a coefficient of determination R2 equal to 0.9686, which argue strongly that ROS are likely responsible for the combined microbicidal activity. The investigation suggests that a combination of aBL and carvacrol could offer a rapid, effective, and safe alternative to conventional antimicrobial therapy for multidrug-resistant microbes.


Tomographic fluorescence and phosphorescence lifetime multiplexing in the spatial frequency domain
Paper 10874-33

Author(s):  Anand T. Kumar, Massachusetts General Hospital (United States), et al.
Conference 10874: Optical Tomography and Spectroscopy of Tissue XIII
Session 7: Fluorescence Imaging
Date and Time: 2/5/2019 2:10:00 PM

The ability to simultaneously recover multiple targets within biological tissue (multiplexing) can have important applications for tracking parallel disease processes in vivo. Here we present a novel method for rapid and quantitative multiplexing within a scattering medium, such as biological tissue, using lifetime contrast. This method is applicable for lifetimes ranging from sub-nanosecond (fluorescence) to micro-second (phosphorescence) timescales. We also show that the SF-ATD approach can exploit selective filtering of high spatial frequencies to dramatically improve reconstruction accuracy for fluorophores with subnanosecond lifetimes, which is typical of most near-infrared fluorophores.


Heat-generating nanocomposite for eradicating bacterial infections associated with indwelling medical implants
Paper 10863-37

Author(s):  Nicole Levi-Polyachenko, Wake Forest Univ. School of Medicine (United States), et al.
Conference 10863: Photonic Diagnosis, Monitoring, Prevention, and Treatment of Infections and Inflammatory Diseases 2019
Session 8: UV irradiation, Photothermal Therapy and Miscellaneous
Date and Time: 2/5/2019 3:30:00 PM

Staphylococcus aureus (SA) is a common pathogenic bacterium prevalent in a wide variety of diseases. One mechanism proposed for mediating SA biofilm-associated infections is to disrupt the polymer structure of the biofilm using heat. For the generation of heat, we have included photothermal donor–acceptor conjugated polymer nanoparticles based on poly[4,4-bis(2-ethylhexyl)-cyclopenta[2,1-b;3,4-b’]dithiophene-2,6-diyl-alt-2,1,3-benzoselenadiazole-4,7-diyl] (PCPDTBSe) into silicone. The composite materials were evaluated for the killing of planktonic and biofilm-residing S. aureus, in either the presence or absence of the antibiotic gentamicin, leading to a 75-100% reduction in viable bacteria. These results demonstrate a photothermal nanocomposite for eliminating SA infections on silicone medical devices.


Eradication of broad-spectrum intracellular bacteria through photoinactivation of a detoxifying enzyme
Paper 10863-38

Author(s):  Pu-Ting Dong, Boston Univ. (United States), et al.
Conference 10863: Photonic Diagnosis, Monitoring, Prevention, and Treatment of Infections and Inflammatory Diseases 2019
Session 8: UV irradiation, Photothermal Therapy and Miscellaneous
Date and Time: 2/5/2019 3:55:00 PM

Multi-drug resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA), P. aeruginosa and Salmonella enterica could cause a wide range of infections from minor subcutaneous infection to toxic shock syndrome, and bacteremia. As the body’s second line of host defense, phagocytosis could eliminate the majority of the invasive bacteria. However, the survival of microbial pathogens within the macrophage cells which act as ‘Trojan horses’ largely provides a reservoir relatively related protected from antibiotics, thus causing recurrent infections from the dissemination of intracellular bacteria. Here, we develop an effective photonic approach to assist macrophage cell (RAW 264.7) to efficiently eradicate intracellular MRSA, P. aeruginosa along with Salmonella enterica through photoinactivation of a detoxifying enzyme.


OCT for core biopsy guidance: a rabbit study
Paper 10873-14

Author(s):  Nicusor V. Iftimia, Physical Sciences Inc. (United States), et al.
Conference 10873: Optical Biopsy XVII: Toward Real-Time Spectroscopic Imaging and Diagnosis
Session 4: Optical Histology II
Date and Time: 2/5/2019 4:00:00 PM

In this paper, we summarize our recent advances in the development and pre-clinical testing of the 2-nd generation OCT-based probe for core needle biopsy guidance. The acquired OCT images are processed in real-time in a GPU unit to provide the interventional radiologist with the capability to examine the tissue cellularity at the tip of the biopsy needle before deciding to take a biopsy core. The extensive testing of this technology on a rabbit model of soft tissue cancer is discussed in detail. The pre-clinical results demonstrate the capability of this OCT-based probe for determining the in situ cellularity of the tissue at the tip of the biopsy needle and thus its potential use for improving the quality of the sampled biopsy cores.


Antibody conjugated oligonucleotides as a platform for cyclic immunofluorescent staining
Paper 10881-32

Author(s):  Nathan McMahon, Oregon Health & Science Univ. (United States), et al.
Conference 10881: Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues XVII
Session 8: Cytomics II
Date and Time: 2/5/2019 4:10:00 PM


Rapid evaluation of prostate tissue surgical specimens using nonlinear microscopy
Paper 10882-51

Author(s):  Lucas C. Cahill, Massachusetts Institute of Technology (United States), et al.
Conference 10882: Multiphoton Microscopy in the Biomedical Sciences XIX
Session 14: Technology Development II
Date and Time: 2/5/2019 4:25:00 PM

An estimated 15% of patients who undergo a radical prostatectomy for prostate cancer have positive surgical margins, which increases the risk of biochemical recurrence, local recurrence and need for adjuvant or salvage therapy. In this study, we demonstrate rapid histological imaging of freshly excised prostate cancer surgical tissue using nonlinear microscopy (NLM). Specimens, which are stained for 2 minutes in fluorescent dyes, are displayed in real-time using an H&E color map and read by a trained genitourinary pathologist. Entire cross-sections of prostates are evaluated in minutes. We present a comparative analysis of NLM and standard paraffin embedded H&E.


Improving intensity-based virtual H&E from fluorescence imaging with deep learning
Paper 10873-17

Author(s):  Faisal Mahmood, Johns Hopkins Univ. (United States), et al.
Conference 10873: Optical Biopsy XVII: Toward Real-Time Spectroscopic Imaging and Diagnosis
Session 4: Optical Histology II
Date and Time: 2/5/2019 5:10:00 PM

Light-sheet microscopy is a tool for high-throughput, volumetric tissue imaging but images and volumes from such a microscope cannot be easily interpreted by pathologists. In this work, we present a deep learning approach based on unsupervised adversarial image-to-image translation to transfer fluorescence light sheet images to pseudo-H&E images. We demonstrate that we can reconstruct pseudo-H&E images with a cumulative structural similarity index of 0.924 and a normalized RMS error of 0.871 calculated between pseudo-H&E images and corresponding registered views of H&E. We also show that there was a 97.3% accuracy between nuclei detected by pseudo-H&E and corresponding H&E images.


Correcting Cherenkov emission attenuation in tissue with spatial frequency domain imaging during whole-breast external beam radiation therapy for the quantitative imaging of dose delivery
Paper 10874-40

Author(s):  Rachael L. Hachadorian, Dartmouth College (United States), et al.
Conference 10874: Optical Tomography and Spectroscopy of Tissue XIII
Session 8: Fluorescence and Cherenkov Radiation
Date and Time: 2/5/2019 5:10:00 PM

Imaging Cherenkov emission during radiotherapy has been developed to establish real-time field verification, in vivo, however, establishing real-time quantitative dosimetry remains a complex problem involving many parameters. To begin correcting for tissue-derived optical attenuation, wide-field spatial frequency domain images (SFDI) were acquired using the Reflect RS (Modulated Imaging Inc.), registered to each cumulative Cherenkov image, and used to generate pixel-by-pixel maps of corrective scale factors. This study corrected for vasculature and decreased local differences (up to 24%) in the imaged field due to highly pigmented regions, lending optimism that quantitative, real-time, in vivo dosimetry may become feasible in near-future works.


Dual mode photoacoustic and ultrasound imaging system based on a Fabry-Perot scanner
Paper 10878-76

Author(s):  Khoa Pham, Univ. College London (United Kingdom), et al.
Conference 10878: Photons Plus Ultrasound: Imaging and Sensing 2019
Session 12: Microscopy and Multimodal Imaging: System and Application II
Date and Time: 2/5/2019 5:45:00 PM

A combined photoacoustic and pulse-echo ultrasound imaging system based on the planar Fabry-Perot scanner, modified with an added capability for optically generating ultrasound, is presented. The modification involved coating the Fabry-Perot ultrasound sensor with a novel Gold-Nanoparticle-PDMS composite which was excited with nanosecond laser pulses to generate plane-wave ultrasound pulses. The system was characterised in terms of its acoustic generation and imaging performance. This novel all-optical system has the potential to add complementary morphological contrast to photoacoustic vascular images which could aid the clinical assessment of superficial tumours, lymph node disease and other conditions.


Multiphoton and harmonic generation imaging methods enable direct visualization of drug nanoparticle in conjunction with vascularity in ex vivo fibrotic prostate tumor mouse model
Paper 10881-64

Author(s):  Thomas Abraham, Penn State College of Medicine (United States), et al.
Conference 10881: Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues XVII
Session PTues: Posters-Tuesday
Date and Time: 2/5/2019 6:00:00 PM

Prostate cancer (PCA) is the most common cancer and the third most common cause of cancer death in men. Targeted nanoparticles (NPs) that deliver effective doses of chemotherapeutic drugs specifically to PCA could improve chemotherapy efficacy without the toxicities. In the relevant mouse models, the direct visualization of such drug nanoparticles along with the vasculature at submicron resolution are critically important for the accurate measurements of the drug distribution in the tissue matrix. Multiphoton microscopy, which uses ultra-short IR laser pulses as the excitation source, produces multiphoton excitation fluorescence (MPEF) signals from exogenous or endogenous fluorescent proteins and induces specific second harmonic generation (SHG) signals from non-centrosymmetric proteins such as fibrillar collagens. The objective here is to visualize and quantify the 3D distribution of an aptamer conjugated calcium phosphosilicate based drug nanoparticle carriers along with vasculature and tissue matrix in ex vivo mouse prostate tumor tissue with submicron resolution. Human prostate tumor xenografts were established in athymic mice by injecting prostate cell line derived from human (PC-3 cells) and were grown for 4 weeks. Near-infrared imaging agent indocyanine green (ICG) loaded calcium phosphosilicate nanoparticles (CPSNPs) including targeted CPSNPs bioconjugated with DNA Aptamer [AP1153], empty non-ICG containing CPSNPs (Ghost) and Dil (for blood vessel painting) were injected into the tail vein. The spectral unmixing was performed to extract Dil signal from ICG signal using measured emission spectra. The 3D reconstructions and subsequent quantitation showed accumulation of ICG in blood capillaries versus tissue matrix. We here conclude that this multiphoton based multimodal imaging approach can provide spatially resolved 3D images with spectral specificities that are sensitive enough to identity and quantify the distributions of drug nanoparticle carriers in conjunction with vasculature and tissue matrix in prostate tumor with structural precision.


Performance validation of improved photoacoustic/ultrasound superposed imaging system for evaluation of diabetic neuropathy
Paper 10878-193

Author(s):  Miya Ishihara, National Defense Medical College (Japan), et al.
Conference 10878: Photons Plus Ultrasound: Imaging and Sensing 2019
Session PTues: Posters-Tuesday
Date and Time: 2/5/2019 6:00:00 PM

We developed the PhotoAcoustic (PA) imaging system which could be realized the fusion of PA and conventional UltraSound (US) image. We successfully observed median and sural nerve bundles with US image, and PA images of blood vessels around and in that nerve bundles. As results of the preliminary clinical trial to patients with type 2 diabetes for the evaluation of diabetic neuropathy, we found two technological challenges to overcome. The system was improved to a combination of 1064 nm and 12 MHz. We verified the performance of the improved prototype PA system using a specially designed rabbit hypoxia model.


In vivo demonstration of photoacoustic-guided liver surgery
Paper 10878-217

Author(s):  Kelley Kempski, Univ. of Delaware (United States), et al.
Conference 10878: Photons Plus Ultrasound: Imaging and Sensing 2019
Session PTues: Posters-Tuesday
Date and Time: 2/5/2019 6:00:00 PM

Photoacoustic imaging is one solution for intraoperative visualization of blood vessels, reducing the risk of accidental injury to an artery or vein. The objective of this study was to determine the feasibility of in vivo vessel visualization to enable photoacoustic-guided liver surgery. Photoacoustic imaging was used to identify blood vessels in the liver of two pigs during a laparotomy. Delay-and-sum beamforming and coherence-based beamforming were used to display photoacoustic images. These results lend insight into the feasibility of photoacoustic-guided liver surgery.


3D printed kidney phantoms for an LED-based photoacoustic and ultrasound imaging system
Paper 10878-228

Author(s):  Daniil I. Nikitichev, Univ. College London (United Kingdom), et al.
Conference 10878: Photons Plus Ultrasound: Imaging and Sensing 2019
Session PTues: Posters-Tuesday
Date and Time: 2/5/2019 6:00:00 PM

Tissue-mimicking anatomical phantoms are vital for evaluation and training purposes. Three-dimensional (3D) printing technology allows direct formation of the patient-specific objects based on medical imaging data. In this work, we developed a novel 3D printer kidney phantom based on Gel Wax for photoacoustic imaging. This phantom has multiple layer structures with different optical and acoustic properties. The phantom was used to evaluate the performance of an LED-based photoacoustic and ultrasound imaging system. The developed phantom has the ability to mimic a kidney both when physically interacting and imaging it. Success in this field would push to apply this method to alternative organs and procedures that would benefit from such phantoms.


Innovative and high-performance instrumentation for biomedical Mueller polarimetric imaging in vivo
Paper 10873-18

Author(s):  Arvid Lindberg, Ecole Polytechnique (France), et al.
Conference 10873: Optical Biopsy XVII: Toward Real-Time Spectroscopic Imaging and Diagnosis
Session 5: Spectroscopic Methods I
Date and Time: 2/6/2019 8:20:00 AM

Mueller Polarimetric Imaging (MPI) has shown very promising results in biomedical applications, especially for detection of precancerous tissues. Extending these results to in vivo characterization remains an instrumental challenge. We show an innovative and pragmatic approach for building full-field MPI systems based on Ferroelectric Liquid Crystals capable of fast multispectral (in the visible range) analysis of biological tissues in vivo, with high accuracy, while using compact components. We constructed a first simultaneous multispectral MPI colposcope for the analysis of the uterine cervix in vivo, as well as a first multispectral MPI laparoscope for use in minimally invasive surgery.


Label-free spectroscopic imaging unravels altered lipid metabolism in human renal cell cancer
Paper 10882-56

Author(s):  Shuhua Yue, Beihang Univ. (China), et al.
Conference 10882: Multiphoton Microscopy in the Biomedical Sciences XIX
Session 15: Nonlinear and Linear Chemical Imaging I
Date and Time: 2/6/2019 8:25:00 AM


Snapshot multi-spectral-line imaging for applications in dermatology and forensics
Paper 10881-39

Author(s):  Janis Spigulis, Univ. of Latvia (Latvia), et al.
Conference 10881: Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues XVII
Session 9: Spectral Imaging I
Date and Time: 2/6/2019 8:30:00 AM

Advanced spectral imaging technique has been developed, implemented in experimental prototype devices and validated for mapping of skin chromophores and for detection of counterfeits. Single spectral line images were extracted from RGB image data cubes at simultaneous illumination of the target by several laser emission lines, e.g. 448 nm, 532 nm and 659 nm. A smartphone-based prototype has been used for mapping of melanin, oxy-hemoglobin and deoxy-hemoglobin in skin malformations and for comparative analysis of valid and counterfeit 20 EUR and 50 EUR banknotes, as well as for counterfeit document detection. The obtained results confirmed promising potential of the proposed imaging technology for both applications.


Deep-learning based automated instrument tracking and adaptive-sampling of intraoperative OCT for video-rate volumetric imaging of ophthalmic surgical maneuvers
Paper 10867-57

Author(s):  Mohamed T. El-Haddad, Vanderbilt Univ. (United States), et al.
Conference 10867: Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XXIII
Session 9: Image and Signal Processing
Date and Time: 2/6/2019 8:30:00 AM

Intraoperative optical coherence tomography (iOCT) enables volumetric imaging of surgical maneuvers. However, the lack of automated instrument-tracking remains a critical barrier to real-time surgical feedback and iOCT-guided surgery. We previously presented spectrally-encoded coherence tomography and reflectometry (SECTR), which provides simultaneous imaging of spatiotemporally co-registered orthogonal imaging planes at several gigapixels-per-second. Here, we demonstrate automated surgical instrument-tracking and adaptive-sampling of OCT using a combination of deep-learning and SECTR. We believe this method overcomes critical barriers to clinical translation of iOCT and offers several computational and system advantages over previous approaches.


A-line based convolutional neural network (CNN) classification of breast cancer in optical coherence tomography (OCT) images
Paper 10867-58

Author(s):  Diana Mojahed, Columbia Univ. (United States), et al.
Conference 10867: Optical Coherence Tomography and Coherence Domain Optical Methods in Biomedicine XXIII
Session 9: Image and Signal Processing
Date and Time: 2/6/2019 8:45:00 AM

The purpose of this study was to develop and evaluate the performance of a convolutional neural network (CNN) that uses a novel A-line based classification approach to detect cancer in OCT images of breast specimens. The proposed algorithm utilized a hybrid 2D/1D convolutional neural network (CNN) to map each single B-scan to a 1D label vector. Each A-line was labelled with one of the following tissue types: ductal carcinoma in situ (DCIS), invasive ductal carcinoma (IDC), adipose, and stroma. Algorithm was also used in a binary classification, combining DCIS and IDC as malignancy, and adipose and stroma as non-malignancy.


Stimulated Raman scattering endoscopy for in vivo label-free histology
Paper 10882-59

Author(s):  Peng Lin, Boston Univ. (United States), et al.
Conference 10882: Multiphoton Microscopy in the Biomedical Sciences XIX
Session 15: Nonlinear and Linear Chemical Imaging I
Date and Time: 2/6/2019 9:30:00 AM

Stimulated Raman scattering (SRS) microscopy enables fast label-free histopathological analysis of the lesions with high specificity by mapping their chemical compositions. However, benchtop SRS microscopy is unable to access tissues of interest in vivo inside the human body. Here, we develop an implantable fiber-scanning SRS endoscope for label-free in vivo histology. The endoscope provides background-free SRS hyperspectral images at C-H and C-D regions by using a home-made micro-objective of high-dispersive ZnSe glass. We expect the innovation to have great potential for broad medical applications such as label-free image-based diagnosis and surgical guidance.


Nanobubble detection using acoustic based flow cytometry
Paper 10878-84

Author(s):  Vaskar Gnyawali, Ryerson Univ. (Canada), et al.
Conference 10878: Photons Plus Ultrasound: Imaging and Sensing 2019
Session 13: Contrast Agents and Molecular Imaging
Date and Time: 2/6/2019 9:30:00 AM

Our acoustic flow cytometer is capable of detecting individual nanobubbles using very-high-frequency ultrasound (center frequency 375 MHz) and photoacoustic waves. The individual nanobubble interacts with the ultrasound and laser pulses in a microfluidic channel to produce interleaved ultrasound backscatter and photoacoustic waves, respectively. Results show that the amplitude the of the ultrasound backscatter is dependent on the size of the nanobubbles.


Ultra-resolution spectral confocal add-on systems for light microscopes
Paper 10881-43

Author(s):  Fartash Vasefi, Spectral Molecular Imaging, Inc. (United States), et al.
Conference 10881: Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues XVII
Session 9: Spectral Imaging I
Date and Time: 2/6/2019 9:50:00 AM

The first confocal microscope was released in 1987. Since then, laser scanning confocal microscopy has been widely used in developmental and molecular biology, and pathology. Currently, there is a growing need to image multiple fluorescent markers, simultaneously and cost-effectively, to detect, discriminate and quantitate various components and their interactions. We developed an affordable ultra-resolution spectral confocal add-on system and tested it on research-grade microscopes. Our system includes supercontinuum laser as a broadband light source, a confocal scanning system, and spectral selection using custom spectral tunable cavities (STCs) offering an ultra-spectral resolution. We present the confocal system images on histopathology slides.


Functional calcium imaging using optical-resolution photoacoustic microscopy in a 3D tumor cell culture
Paper 10878-86

Author(s):  Wei-Wen Liu, National Taiwan Univ. (Taiwan), et al.
Conference 10878: Photons Plus Ultrasound: Imaging and Sensing 2019
Session 13: Contrast Agents and Molecular Imaging
Date and Time: 2/6/2019 10:00:00 AM

To achieve a sufficient penetration depth to visualize calcium dynamics in a 3D tumor cell culture, the contrast agent, Chlorophosphonazo-III (CPZ), is evaluated using optical-resolution photoacoustic microscopy. High correlation with the photoacoustic (PA) signal intensity and the calcium concentration in the range of 0.025 to 2 mM demonstrates the feasibility of using CPZ-dependent PA calcium imaging at 627 nm. Furthermore, a 2-fold enhancement of PA intensity measured by using live-cell PA calcium imaging demonstrates that functional calcium imaging can be implemented when stimulating 3D tumorspheres with thapsigargin and high concentration of extracellular calcium.


Dark-field hyperspectral imaging of single plasmonic gold nanorods and their scattering characteristics in complex biological environments
Paper 10881-44

Author(s):  Nishir S. Mehta, Louisiana State Univ. (United States), et al.
Conference 10881: Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues XVII
Session 10: Spectral Imaging II
Date and Time: 2/6/2019 10:40:00 AM

Adipose tissue-derived stem cells (ASCs) has applications in soft tissue replacement-based tissue engineering. A method to facilitate long-term tracking of the cells will enable a better understanding of stem cell fate in stem cell-based therapeutics. Hyperspectral microscopy combining both nanoscale imaging and spectral characteristics from plasmonic nanostructures provides a powerful tool for their identification and quantitative spectral analysis of plasmonic nanostructures with an unprecedented level of details. The analysis and utility of gold nanorods for labeling stem cells and the orientation dependent spectral features of nanorods inside the cells are characterized and discussed in detail. The cell viability, differentiation capacity, gene expression, potential cytotoxicity due to nanorods such as inflammatory molecule and reactive oxygen species production, the adipogenic and osteogenic potential will be evaluated using histochemical staining and quantitative polymerase chain reaction (qPCR). The study has implications towards tracking individual nanorods in complex biological systems and beyond.


Photoacoustic spectral analysis at ultraviolet wavelength for assessing the aggressiveness of prostate cancer
Paper 10878-88

Author(s):  Guan Xu, Univ. of Michigan (United States), et al.
Conference 10878: Photons Plus Ultrasound: Imaging and Sensing 2019
Session 14: Quantitative Analysis and Imaging
Date and Time: 2/6/2019 11:00:00 AM

The aggressiveness of Prostate cancer (PCa) is quantified under a Gleason grading system, which describes the cellular level architectural heterogeneity of the prostate tissue. The strong optical absorbing properties of cell nuclei at ultraviolet (UV) wavelengths provides a unique opportunity for quantifying the PCa architectures, i.e. Gleason patterns, using photoacoustic spectral analysis (PASA) in vivo. Statistical significance was observed between the normal and cancerous mice, and between the cancerous mice at progressive stages. Ex vivo measurement with human PCa tissue using the same method has shown a correlation of 0.89 between the PASA quantification and the Gleason grades.


Cerebral blood flow measurement in adults during hypercapnia using continuous wave and time domain diffuse correlation spectroscopy
Paper 10874-48

Author(s):  Stefan A. Carp, Athinoula A. Martinos Ctr. for Biomedical Imaging (United States), et al.
Conference 10874: Optical Tomography and Spectroscopy of Tissue XIII
Session 10: Cerebral Blood Flow
Date and Time: 2/6/2019 11:10:00 AM

Cerebral blood flow assessment using non-invasive diffuse correlation spectroscopy techniques offers the potential to improve critical care for patients undergoing procedures that may impact brain health. In this work we characterize the performance of continuous wave (CW) and time domain (TD) diffuse correlation spectroscopy measurements in assessing cerebral blood flow through measurements on several healthy volunteers during CO2 inhalation. We report on the noise performance and cerebral sensitivity of the two DCS approaches, as well as compare the optical blood flow change estimates with MRI arterial spin labeling data.


Comparison of breast tumor size by intraoperative photoacoustic tomography, magnetic resonance imaging and pathology
Paper 10878-90

Author(s):  Ivan Kosik, Western Univ. (Canada), et al.
Conference 10878: Photons Plus Ultrasound: Imaging and Sensing 2019
Session 14: Quantitative Analysis and Imaging
Date and Time: 2/6/2019 11:30:00 AM

Due to its superior molecular sensitivity, surgical management of breast cancer now often includes preoperative dynamic contrast enhanced magnetic resonance imaging (DCE-MRI). Nevertheless, statistics indicate that, in practice, tumor size is frequently misestimated leading to incomplete resections, and consequently, repeat surgeries. Our group developed a surgical specimen scanner based on intraoperative photoacoustic tomography (iPAT) with the capability to visualize whole breast tumors. The system was deployed at a breast surgical center and used to scan freshly excised breast tissue specimens belonging to 12 patients. This report compares breast cancer imaging performance by iPAT to that of DCE-MRI, and pathology.


Machine learning assisted blood vessel segmentation in laser speckle imaging
Paper 10873-27

Author(s):  Vyacheslav Kalchenko, Weizmann Institute of Science (Israel), et al.
Conference 10873: Optical Biopsy XVII: Toward Real-Time Spectroscopic Imaging and Diagnosis
Session 6: Spectroscopic Methods II
Date and Time: 2/6/2019 11:40:00 AM

We are introducing an application of a machine learning approach for express analysis of Laser Speckle (LS) images. This application can be utilized for real-time visualization of vascular beds in vivo. This research used Waikato Environment for Knowledge Analysis (Weka) integrated with Fiji/ImageJ software. A large number of acquired LS images are averaged, then used as references for training Weka classifiers. Subsequently, a bundle of these Weka classifiers are produced. We defined the minimal number of raw LS images based on a phenomenological model to minimize the time needed for LS data analysis. Finally, a new perceptually uniform color coding approach is developed for highlighting targeted blood vessels. The developed LS processing approach is especially convenient, because of its high potential for blood vessel visualization during real-time intraoperative vascular imaging in vivo.


Photoacoustic imaging of RF ablation lesion formation in an ex-vivo passive beating porcine heart model
Paper 10878-93

Author(s):  Sophinese Iskander-Rizk, Erasmus MC (Netherlands), et al.
Conference 10878: Photons Plus Ultrasound: Imaging and Sensing 2019
Session 15: Monitoring of Therapy
Date and Time: 2/6/2019 1:45:00 PM

One of the treatments of atrial fibrillation is RF ablation. During this procedure, undesired tissue conductivity is interrupted by inducing scar tissue through applying RF current. Feedback on created lesions is currently indirect, leading to unpredictable outcomes: ~40% of procedures need one or more re-intervention(s) for success. Here, we propose ablation monitoring with photoacoustic imaging (PA). We fit the ablation catheter with an optical fiber for light delivery and receive the PA signal using an intracardiac echo probe. In this study we show feasibility of real-time visual feedback on lesion progression with dual-wavelength PA in a porcine beating heart model.


Slide-free molecular histopathology using simultaneous label-free auto-fluorescence multi-harmonic (SLAM) microscopy
Paper 10882-73

Author(s):  Stephen Allen Boppart, Univ. of Illinois (United States), et al.
Conference 10882: Multiphoton Microscopy in the Biomedical Sciences XIX
Session 18: Nonlinear and Linear Chemical Imaging IV
Date and Time: 2/6/2019 4:10:00 PM

Histopathology has been the gold-standard process for the diagnosis of disease. By generating new excitation wavelengths and manipulating the light stimulus in new ways, Simultaneous Label-free Auto-fluorescence Multi-harmonic (SLAM) microscopy can achieve fast and simultaneous visualization of the rich intrinsic molecular, metabolic, and structural information within fresh tissues and during in vivo procedures. Results suggest the broad potential of this technology and methodology for digital pathology applications, and for identifying molecular and metabolic signatures and tumor-associated extracellular vesicles in fresh, untreated tissue specimens that may have diagnostic value and help elucidate their physiological roles in cancer progression.


Widefield measurements of water and lipids with label-free short-wave spatial frequency domain imaging
Paper 10873-35

Author(s):  Darren M. Roblyer, Boston Univ. (United States), et al.
Conference 10873: Optical Biopsy XVII: Toward Real-Time Spectroscopic Imaging and Diagnosis
Session 8: SWIR and IR Methods II
Date and Time: 2/6/2019 4:30:00 PM

Widefield near-infrared (NIR) diffuse optical imaging can provide molecular and microstructural contrasts without the use of exogenous agents. Our group is developing methods to increase the molecular contrast of widefield diffuse imaging by extending the measurement spectral bandwidth to the Short Wave Infrared (SWIR): 900 – 1300 nm. The SWIR wavelength band provides improved molecular sensitivity to distinct lipid species, water, and collagen, and improved optical depth of penetration compared to the NIR, due to reduced scattering. By illuminating the tissue surface with spatially modulated light, absolute chromophore concentrations can be extracted through the technique known as Spatial Frequency Domain Imaging (SFDI). We will present data showing that SWIR SFDI can be used to monitor inflammation-induced edema, provide spatial mapping of water/lipid heterogeneity in tumors, discriminate brown from white fat in vivo, and non-invasively monitor lipids in human subjects after a high-fat meal. For example, we identified brown adipose tissue through intact skin in mice with an 88% accuracy, demonstrating the potential for applications in obesity and thermoregulation. Additionally, we conducted a study in human normal volunteers that demonstrated the ability to non-invasively track blood lipid content in vascular and avascular tissue compartments. We found a strong correlation between our non-invasive measurements and blood draws (rho=0.67). We will also show how time-multiplexed SFDI can provide faster and more robust hyperspectral data sets, increasing throughput for preclinical testing and reducing barriers to clinical implementation.


Diffuse optical spectroscopic imaging reveals dose and schedule dependent changes in breast tumors throughout neoadjuvant chemotherapy
Paper 10874-58

Author(s):  Anup Tank, Boston Univ. (United States), et al.
Conference 10874: Optical Tomography and Spectroscopy of Tissue XIII
Session 12: Breast Imaging
Date and Time: 2/6/2019 4:40:00 PM

Diffuse Optical Spectroscopic Imaging (DOSI) can provide label-free information about breast tumors during neoadjuvant chemotherapy (NAC). We will show for the first time that DOSI response parameters are dependent on the specific NAC regimen used. 54 subjects were included in this analysis. Subjects were given either a Maximum Tolerated Dose (MTD) or a Metronomic (MET) regimen. Week 1 oxyhemoglobin flare was prognostic for MTD subjects but did not manifest in MET subjects. Lipid and hemoglobin normalization at midpoint was prognostic for both cohorts. This study indicates that the specific regimen must be considered when using DOSI for NAC monitoring.


A novel method for scatterers type enumeration in polydisperse suspensions through fiber trapping and unsupervised scattering analysis
Paper 10881-58

Author(s):  Joana S. Paiva, INESC TEC (Portugal), et al.
Conference 10881: Imaging, Manipulation, and Analysis of Biomolecules, Cells, and Tissues XVII
Session 12: Bioinformatics
Date and Time: 2/6/2019 5:20:00 PM

With the advent of Microfluidics, there is a need to characterize suspensions, mainly regarding composition variability. However, the state-of-the-art techniques are complex. We propose a novel, fast and portable method to determine the number of scatterers type present in a suspension. It uses features derived from the back-scattered signal acquired through a spherical-lensed optical fiber tip dipped into the solution under test and unsupervised learning. This method has correctly determined the number of particle types present in different suspensions containing synthetic particles and yeasts; bacteria; and nanoparticles types. This could be a valuable alternative to complex and time-consuming techniques.


Three-dimensional breast shape acquisition and co-registration method for multimodal dynamic DOT and digital breast tomosynthesis
Paper 10874-60

Author(s):  Bin Deng, Athinoula A. Martinos Ctr. for Biomedical Imaging (United States), et al.
Conference 10874: Optical Tomography and Spectroscopy of Tissue XIII
Session 12: Breast Imaging
Date and Time: 2/6/2019 5:20:00 PM

The ill-posed nature of the DOT inverse problem makes this technique particularly susceptible to model errors when the data-acquisition conditions do not fully match the assumptions built into the image reconstruction process. In this paper, we describe the use of a set of auxiliary devices in conjunction to a multimodal DOT/x-ray system to capture accurate breast shape information and a 3D surface registration method that spatially co-registers separately acquired clinical DBT scans with DOT measurements for guided optical image reconstruction. We demonstrate the performance of this method by imaging patients presenting with benign or malignant lesions during stepwise breast compression.